Reduced Ca2+ATPase levels contribute to many diseases including cardiovascular disease, high blood pressure, cancer, obesity, diabetes, and brain dysfunction.

Many toxins such as pesticides, mercury, lead, fluoride, fire retardants, bisphenol, food additives, food dyes and dietary states such as hyperglycemia reduce Ca2+ATPase.

Most importantly, you can help to maintain healthy Ca2+ATPase levels by reducing your exposure to many of the toxins that reduce Ca2+ATPase. In addition to avoiding toxins, controlling your blood sugar, exercising and choosing specific supplements such as green tea, ginger, and vitamin E can support Ca2+ATPase levels.



Ca2+ATPase is an enzyme found in every cell in the body whose job it is to regulate intracellular calcium. Intracellular calcium is simply the level of calcium within the cells.

What is intracellular calcium?

The body contains approximately 2.2 pounds of calcium in total. 99.5 % of this resides in bones, tissues and teeth (which is likely the calcium you are most familiar with.) The remaining 0.5% of calcium circulates within the blood stream available for use by the cells. This calcium is used by the cells to trigger actions. A rise in intracellular calcium triggers an event to happen.

For example:
1. In muscle cells, a rise in intracellular calcium triggers muscle contraction.
2. In cardiac cells a rise in intracellular calcium triggers the heart to beat.
3. In brain cells, a rise in intracellular calcium triggers neurotransmitter release.

Once the event has occurred, Ca2+ATPase helps return intracellular calcium levels back to resting levels. It does this by pumping excess calcium into storage compartments within the cells. The storage compartment is called the sarcoplasmic or endoplasmic reticulum depending on what type of cell it is.

Why are intracellular calcium levels important?

If you continue the metaphor used in the video below of intracellular calcium serving as a traffic light, imagine if the traffic signals in a city were not working properly. You can imagine the potential problems that this could cause. Then imagine the millions of processes controlled by intracellular calcium in your body every second, every minute, of every day. When calcium levels go awry, we become significantly more susceptible to disease.


Learn about the relationship between reduced Ca²⁺ATPase and numerous chronic diseases.


  • Ca²⁺ATPase is responsible for approximately 40% of calories burned by your muscles and approximately 12-15% of total calories burned.

Skeletal Muscle Thermogenesis and Its Role in Whole Body Energy Metabolism.
Periasamy M, Herrera JL, Reis FCG.
Diabetes Metab J. 2017 Oct;41(5):327-336. doi: 10.4093/dmj.2017.41.5.327. Review.

Role of SERCA Pump in Muscle Thermogenesis and Metabolism.
Periasamy M, Maurya SK, Sahoo SK, Singh S, Sahoo SK, Reis FCG, Bal NC.
Compr Physiol. 2017 Jun 18;7(3):879-890. doi: 10.1002/cphy.c160030. Review.

Influence of long-term obesity on myocardial gene expression.
Lima-Leopoldo AP, Leopoldo AS, Silva DC, Nascimento AF, Campos DH, Luvizotto Rde A, Oliveira Júnior SA, Padovani CR, Nogueira CR, Cicogna AC.
Arq Bras Cardiol. 2013 Mar;100(3):229-37. English, Portuguese.

Early cardiovascular changes occurring in diet-induced, obese insulin-resistant rats.
Huisamen B, Dietrich D, Bezuidenhout N, Lopes J, Flepisi B, Blackhurst D, Lochner A.
Mol Cell Biochem. 2012 Sep;368(1-2):37-45. doi: 10.1007/s11010-012-1340-9. Epub 2012 May 26.

Role of sarco/endoplasmic reticulum Ca(2+)-ATPase in thermogenesis.
de Meis L, Arruda AP, Carvalho DP.
Biosci Rep. 2005 Jun-Aug;25(3-4):181-90. Review.

Calcium and magnesium ATPase activities in women with varying BMIs.
Nasser JA, Hashim SA, Lachance PA.
Obes Res. 2004 Nov;12(11):1844-50.

Role of the sarcoplasmic reticulum Ca2+-ATPase on heat production and thermogenesis.
de Meis L.
Biosci Rep. 2001 Apr;21(2):113-37. Review.


  • High blood sugar associated with diabetes reduces Ca²⁺ATPase levels. This reduction in Ca²⁺ATPase is the primary driver of diabetes-related diseases, including heart disease, high blood pressure, eye damage, and nerve damage.

Dapagliflozin rescues endoplasmic reticulum stress-mediated cell death.
Shibusawa R, Yamada E, Okada S, Nakajima Y, Bastie CC, Maeshima A, Kaira K, Yamada M.
Sci Rep. 2019 Jul 8;9(1):9887. doi: 10.1038/s41598-019-46402-6.

Endoplasmic reticulum stress contributes to NMDA-induced pancreatic β-cell dysfunction in a CHOP-dependent manner.
Huang XT, Liu W, Zhou Y, Sun M, Sun CC, Zhang CY, Tang SY.
Life Sci. 2019 Jun 28:116612. doi: 10.1016/j.lfs.2019.116612. [Epub ahead of print]

Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells.
Cnop M, Toivonen S, Igoillo-Esteve M, Salpea P.
Mol Metab. 2017 Jul 12;6(9):1024-1039. doi: 10.1016/j.molmet.2017.06.001. eCollection 2017 Sep. Review.

SERCA2 Deficiency Impairs Pancreatic β-Cell Function in Response to Diet-Induced Obesity.
Tong X, Kono T, Anderson-Baucum EK, Yamamoto W, Gilon P, Lebeche D, Day RN, Shull GE, Evans-Molina C.
Diabetes. 2016 Oct;65(10):3039-52. doi: 10.2337/db16-0084. Epub 2016 Aug 3.

Sarcoplasmic reticulum Ca2+ ATPase pump is a major regulator of glucose transport in the healthy and diabetic heart.
Waller AP, Kalyanasundaram A, Hayes S, Periasamy M, Lacombe VA.
Biochim Biophys Acta. 2015 May;1852(5):873-81. doi: 10.1016/j.bbadis.2015.01.009. Epub 2015 Jan 20.

Inhibition of diabetic-cataract by vitamin K1 involves modulation of hyperglycemia-induced alterations to lens calcium homeostasis.
Sai Varsha MK, Raman T, Manikandan R.
Exp Eye Res. 2014 Nov;128:73-82. doi: 10.1016/j.exer.2014.09.007. Epub 2014 Sep 23.

Advanced glycation end product cross-link breaker attenuates diabetes-induced cardiac dysfunction by improving sarcoplasmic reticulum calcium handling.
Kranstuber AL, Del Rio C, Biesiadecki BJ, Hamlin RL, Ottobre J, Gyorke S, Lacombe VA.
Front Physiol. 2012 Jul 19;3:292. doi: 10.3389/fphys.2012.00292. eCollection 2012.

Sensory neurons derived from diabetic rats have diminished internal Ca2+ stores linked to impaired re-uptake by the endoplasmic reticulum.
Zherebitskaya E, Schapansky J, Akude E, Smith DR, Van der Ploeg R, Solovyova N, Verkhratsky A, Fernyhough P.
ASN Neuro. 2012 Jan 18;4(1). pii: e00072. doi: 10.1042/AN20110038.

Sarco(endo)plasmic reticulum Ca2+-ATPase 2b is a major regulator of endoplasmic reticulum stress and glucose homeostasis in obesity.
Park SW, Zhou Y, Lee J, Lee J, Ozcan U.
Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19320-5. doi: 10.1073/pnas.1012044107. Epub 2010 Oct 25.

Cardiac contractile dysfunction during acute hyperglycemia due to impairment of SERCA by polyol pathway-mediated oxidative stress.
Tang WH, Cheng WT, Kravtsov GM, Tong XY, Hou XY, Chung SK, Chung SS.
Am J Physiol Cell Physiol. 2010 Sep;299(3):C643-53. doi: 10.1152/ajpcell.00137.2010. Epub 2010 Jun 23.

Intracellular Ca2+ regulating proteins in vascular smooth muscle cells are altered with type 1 diabetes due to the direct effects of hyperglycemia.
Searls YM, Loganathan R, Smirnova IV, Stehno-Bittel L.
Cardiovasc Diabetol. 2010 Feb 1;9:8. doi: 10.1186/1475-2840-9-8.

Hyperglycemia-induced alterations in synaptosomal membrane fluidity and activity of membrane bound enzymes: beneficial effect of N-acetylcysteine supplementation.
Kamboj SS, Chopra K, Sandhir R.
Neuroscience. 2009 Aug 18;162(2):349-58. doi: 10.1016/j.neuroscience.2009.05.002. Epub 2009 May 6.

The mechanisms of calcium homeostasis and signalling in the lens.
Rhodes JD, Sanderson J.
Exp Eye Res. 2009 Feb;88(2):226-34. doi: 10.1016/j.exer.2008.10.025. Epub 2008 Nov 18. Review.

Mitochondrial malfunction and Ca2+ dyshomeostasis drive neuronal pathology in diabetes.
Verkhratsky A, Fernyhough P.
Cell Calcium. 2008 Jul;44(1):112-22. doi: 10.1016/j.ceca.2007.11.010. Epub 2008 Jan 11. Review.

In vivo and in vitro effects of hyperglycemia on Na+ -K+, Ca+2, Mg+2-dependent ATPases activity in brain synaptosomes of aging rats.
Torlińska K, Grochowalska A, Kupsz J, Skoracka J, Kojo S.
J Physiol Pharmacol. 2006 Nov;57 Suppl 7:145-58.

Regulation of insulin biosynthesis in pancreatic beta cells by an endoplasmic reticulum-resident protein kinase IRE1.
Lipson KL, Fonseca SG, Ishigaki S, Nguyen LX, Foss E, Bortell R, Rossini AA, Urano F.
Cell Metab. 2006 Sep;4(3):245-54.

Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities.
Cnop M, Welsh N, Jonas JC, Jörns A, Lenzen S, Eizirik DL.
Diabetes. 2005 Dec;54 Suppl 2:S97-107. Review.

Axon degeneration mechanisms: commonality amid diversity.
Coleman M.
Nat Rev Neurosci. 2005 Nov;6(11):889-98. Review.

Diabetes-induced decrease in rat brain microsomal Ca2+-ATPase activity.
Doğru Pekiner B, Daş Evcimen N, Nebioğlu S.
Cell Biochem Funct. 2005 Jul-Aug;23(4):239-43.

Increased inhibition of SERCA2 by phospholamban in the type I diabetic heart.
Vasanji Z, Dhalla NS, Netticadan T.
Mol Cell Biochem. 2004 Jun;261(1-2):245-9.

Diabetes increases formation of advanced glycation end products on Sarco(endo)plasmic reticulum Ca2+-ATPase.
Bidasee KR, Zhang Y, Shao CH, Wang M, Patel KP, Dincer UD, Besch HR Jr.
Diabetes. 2004 Feb;53(2):463-73.

Impact of endoplasmic reticulum stress pathway on pancreatic beta-cells and diabetes mellitus.
Araki E, Oyadomari S, Mori M.
Exp Biol Med (Maywood). 2003 Nov;228(10):1213-7. Review.

Diabetes and the accompanying hyperglycemia impairs cardiomyocyte calcium cycling through increased nuclear O-GlcNAcylation.
Clark RJ, McDonough PM, Swanson E, Trost SU, Suzuki M, Fukuda M, Dillmann WH.
J Biol Chem. 2003 Nov 7;278(45):44230-7. Epub 2003 Aug 26.

Determination of Ca2+-atpase activity in streptozotocin-induced diabetic rat liver.
Pekiner BD, Daş EN, Nebioğlu S.
Diabetes Nutr Metab. 2002 Apr;15(2):116-20.

Depressed levels of Ca2+-cycling proteins may underlie sarcoplasmic reticulum dysfunction in the diabetic heart.
Netticadan T, Temsah RM, Kent A, Elimban V, Dhalla NS.
Diabetes. 2001 Sep;50(9):2133-8.

Calcium cell signalling and cataract: role of the endoplasmic reticulum.
Duncan G, Wormstone IM.
Eye (Lond). 1999 Jun;13 ( Pt 3b):480-3. Review.

Mechanisms through which high glucose concentration raises [Ca2+]i in renal proximal tubular cells.
Symonian M, Smogorzewski M, Marcinkowski W, Krol E, Massry SG.
Kidney Int. 1998 Oct;54(4):1206-13.

The effect of glucose and calcium on Ca2+-adenosine triphosphatase in pancreatic islets isolated from a normal and a non-insulin-dependent diabetes mellitus rat model.
Levy J, Zhu Z, Dunbar JC.
Metabolism. 1998 Feb;47(2):185-9.

Cellular Ca2+ ATPase activity in diabetes mellitus.

Spieker C, Fischer S, Zierden E, Schlüter H, Tepel M, Zidek W.
Horm Metab Res. 1994 Nov;26(11):544-7.

Decreased Ca2(+)-ATPase activity after glycosylation of erythrocyte membranes in vivo and in vitro.
González Flecha FL, Bermúdez MC, Cédola NV, Gagliardino JJ, Rossi JP.
Diabetes. 1990 Jun;39(6):707-11.

Influence of hyperglycemia on Ca2+-Mg2+ -ATPase of red blood cells from diabetic patients.
Schaefer W, Beeker J, Gries FA.
Klin Wochenschr. 1988 May 16;66(10):443-6.


  • Ca²⁺ATPase has an impact on the growth and differentiation of cancer cells, contributing to cancer’s progression.

Toxic effects of TiO2 nanoparticles in primary cultured rat sertoli cells are mediated via a dysregulated Ca2+ /PKC/p38 MAPK/NF-κB cascade.
Ye L, Hong F, Ze X, Li L, Zhou Y, Ze Y.
J Biomed Mater Res A. 2017 May;105(5):1374-1382. doi: 10.1002/jbm.a.36021. Epub 2017 Feb 24.

Cardiac inflammation involving in PKCε or ERK1/2-activated NF-κB signalling pathway in mice following exposure to titanium dioxide nanoparticles.
Yu X, Hong F, Zhang YQ.
J Hazard Mater. 2016 Aug 5;313:68-77. doi: 10.1016/j.jhazmat.2016.03.088. Epub 2016 Mar 31.

Histone deacetylase inhibitors promote the expression of ATP2A3 gene in breast cancer cell lines.
Contreras-Leal E, Hernández-Oliveras A, Flores-Peredo L, Zarain-Herzberg Á, Santiago-García J.
Mol Carcinog. 2016 Oct;55(10):1477-85. doi: 10.1002/mc.22402. Epub 2015 Sep 1.

TiO2 Nanoparticle Exposure Decreases Spermatogenesis via Biochemical Dysfunctions in the Testis of Male Mice.
Hong F, Si W, Zhao X, Wang L, Zhou Y, Chen M, Ge Y, Zhang Q, Wang Y, Zhang J.
J Agric Food Chem. 2015 Aug 12;63(31):7084-92. doi: 10.1021/acs.jafc.5b02652. Epub 2015 Aug 3.

Suppression of neurite outgrowth of primary cultured hippocampal neurons is involved in impairment of glutamate metabolism and NMDA receptor function caused by nanoparticulate TiO2.
Hong F, Sheng L, Ze Y, Hong J, Zhou Y, Wang L, Liu D, Yu X, Xu B, Zhao X, Ze X.
Biomaterials. 2015 Jun;53:76-85. doi: 10.1016/j.biomaterials.2015.02.067. Epub 2015 Mar 9.

UVB irradiation enhances TiO2 nanoparticle-induced disruption of calcium homeostasis in human lens epithelial cells.
Wu Q, Guo D, Du Y, Liu D, Wang D, Bi H.
Photochem Photobiol. 2014 Nov-Dec;90(6):1324-31. doi: 10.1111/php.12322. Epub 2014 Sep 9.

Zinc oxide nanoparticles inhibit Ca2+-ATPase expression in human lens epithelial cells under UVB irradiation.
Wang D, Guo D, Bi H, Wu Q, Tian Q, Du Y.
Toxicol In Vitro. 2013 Dec;27(8):2117-26. doi: 10.1016/j.tiv.2013.09.015. Epub 2013 Sep 20.

Cardiac-specific overexpression of metallothionein rescues against cigarette smoking exposure-induced myocardial contractile and mitochondrial damage.
Hu N, Han X, Lane EK, Gao F, Zhang Y, Ren J.
PLoS One. 2013;8(2):e57151. doi: 10.1371/journal.pone.0057151. Epub 2013 Feb 19.

Altered Endoplasmic Reticulum Calcium Pump Expression during Breast Tumorigenesis.
Papp B, Brouland JP.
Breast Cancer (Auckl). 2011;5:163-74. doi: 10.4137/BCBCR.S7481. Epub 2011 Jul 14.

Neurotoxicological effects and the impairment of spatial recognition memory in mice caused by exposure to TiO2 nanoparticles.
Hu R, Gong X, Duan Y, Li N, Che Y, Cui Y, Zhou M, Liu C, Wang H, Hong F.
Biomaterials. 2010 Nov;31(31):8043-50. doi: 10.1016/j.biomaterials.2010.07.011. Epub 2010 Aug 7.

Altered Ca2+-homeostasis of cisplatin-treated and low level resistant non-small-cell and small-cell lung cancer cells.
Schrödl K, Oelmez H, Edelmann M, Huber RM, Bergner A.
Cell Oncol. 2009;31(4):301-15. doi: 10.3233/CLO-2009-0472.

Endoplasmic reticulum Ca2+-homeostasis is altered in Small and non-small Cell Lung Cancer cell lines.
Bergner A, Kellner J, Tufman A, Huber RM.
J Exp Clin Cancer Res. 2009 Feb 24;28:25. doi: 10.1186/1756-9966-28-25.

The influence of smoking on semen quality, seminal microelements and Ca2+-ATPase activity among infertile and fertile men.
Kumosani TA, Elshal MF, Al-Jonaid AA, Abduljabar HS.
Clin Biochem. 2008 Oct;41(14-15):1199-203. doi: 10.1016/j.clinbiochem.2008.07.013. Epub 2008 Aug 5.

Alterations in the ATP2A2 gene in correlation with colon and lung cancer.
Korosec B, Glavac D, Rott T, Ravnik-Glavac M.
Cancer Genet Cytogenet. 2006 Dec;171(2):105-11.

The loss of sarco/endoplasmic reticulum calcium transport ATPase 3 expression is an early event during the multistep process of colon carcinogenesis.
Brouland JP, Gélébart P, Kovàcs T, Enouf J, Grossmann J, Papp B.
Am J Pathol. 2005 Jul;167(1):233-42.

Effect of bacoside A on membrane-bound ATPases in the brain of rats exposed to cigarette smoke.
Anbarasi K, Vani G, Balakrishna K, Devi CS.
J Biochem Mol Toxicol. 2005;19(1):59-65.

Sarcoendoplasmic reticulum Ca(2+) ATPase type 2 downregulated in human oral squamous cell carcinoma.
Endo Y, Uzawa K, Mochida Y, Shiiba M, Bukawa H, Yokoe H, Tanzawa H.
Int J Cancer. 2004 Jun 10;110(2):225-31.

Differential regulation of calcium homeostasis in adenocarcinoma cell line A549 and its Taxol-resistant subclone.
Padar S, van Breemen C, Thomas DW, Uchizono JA, Livesey JC, Rahimian R.
Br J Pharmacol. 2004 May;142(2):305-16. Epub 2004 Apr 5.

Squamous cell tumors in mice heterozygous for a null allele of Atp2a2, encoding the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 Ca2+ pump.
Liu LH, Boivin GP, Prasad V, Periasamy M, Shull GE.
J Biol Chem. 2001 Jul 20;276(29):26737-40. Epub 2001 Jun 1.

Benzophenone-sensitized photooxidation of sarcoplasmic reticulum membranes: site-specific modification of the Ca(2+)-ATPase.
Krainev AK, Viner RI, Bigelow DJ.
Free Radic Biol Med. 1997;23(7):1009-20.

Effect of huoxuequyu recipe on erythrocyte ultrastructure and membrane ATPase activity in rats with passive smoking.
Chen Z, Jiao X, Yang F, Wu H, Shu H.
J Tongji Med Univ. 1996;16(4):220-2.

Blood Pressure

  • Reduced Ca²⁺ATPase makes it harder for the arteries to relax resulting in constriction or narrowing of arteries. The narrowing of the arteries leads to high blood pressure.

Erythrocyte and plasma Ca2+, Mg2+ and cell membrane adenosine triphosphatase activity in patients with essential hypertension.
Fu Y, Wang S, Lu Z, Li H, Li S.
Chin Med J (Engl). 1998 Feb;111(2):147-9.

Sustained contraction to angiotensin II and impaired Ca2+-sequestration in the smooth muscle of stroke-prone spontaneously hypertensive rats.
Mizuno H, Ikeda M, Harada M, Onda T, Tomita T.
Am J Hypertens. 1999 Jun;12(6):590-5.

The mechanism of Ca2+i increase in blood cells of spontaneously hypertensive rats.
Bruschi G, Bruschi ME, Cavatorta A, Borghetti A.
J Cardiovasc Pharmacol. 1986;8 Suppl 8:S139-44.

Cytoplasmic free [Ca2+] is increased in the platelets of spontaneously hypertensive rats and essential hypertensive patients.
Bruschi G, Bruschi ME, Caroppo M, Orlandini G, Spaggiari M, Cavatorta A.
Clin Sci (Lond). 1985 Feb;68(2):179-84.

Correlation of platelet calcium with blood pressure. Effect of antihypertensive therapy.
Erne P, Bolli P, Bürgisser E, Bühler FR.
N Engl J Med. 1984 Apr 26;310(17):1084-8.

Free calcium concentration in platelets closely relates to blood pressure in normal and essentially hypertensive subjects.
Erne P, Bürgisser E, Bolli P, Ji BH, Bühler FR.
Hypertension. 1984 Mar-Apr;6(2 Pt 2):I166-9.

Heart Failure

  • Heart failure occurs when the heart does not pump sufficiently and inadequate oxygen and nutrients are delivered to the cells. Ca²⁺ATPase plays a key role in the ability of the heart to pump. According to numerous studies, reduced Ca²⁺ATPase is a hallmark of heart failure.

Read more about recent studies showing the link between increased levels of Ca2+ATPase and a reduced risk of heart failure on my blog: https://www.brundebroady.com/new-hope-for-heart-failure-patients/

Modulation of vascular sarco/endoplasmic reticulum calcium ATPase in cardiovascular pathophysiology.
Adachi T.
Adv Pharmacol. 2010;59:165-95. doi: 10.1016/S1054-3589(10)59006-9. Review.

Regulation of sarcoplasmic reticulum Ca2+ ATPase pump expression and its relevance to cardiac muscle physiology and pathology.
Periasamy M, Bhupathy P, Babu GJ.
Cardiovasc Res. 2008 Jan 15;77(2):265-73. Epub 2007 Oct 30. Review.

Regulation of the sarcoplasmic reticulum Ca2+-ATPase expression in the hypertrophic and failing heart.

Zarain-Herzberg A.

Can J Physiol Pharmacol. 2006 May;84(5):509-21. Review.

Accelerated onset of heart failure in mice during pressure overload with chronically decreased SERCA2 calcium pump activity.
Schultz Jel J, Glascock BJ, Witt SA, Nieman ML, Nattamai KJ, Liu LH, Lorenz JN, Shull GE, Kimball TR, Periasamy M.
Am J Physiol Heart Circ Physiol. 2004 Mar;286(3):H1146-53. Epub 2003 Nov 20.

Down-regulation of L-type calcium channel and sarcoplasmic reticular Ca(2+)-ATPase mRNA in human atrial fibrillation without significant change in the mRNA of ryanodine receptor, calsequestrin and phospholamban: an insight into the mechanism of atrial electrical remodeling.
Lai LP, Su MJ, Lin JL, Lin FY, Tsai CH, Chen YS, Huang SK, Tseng YZ, Lien WP.
J Am Coll Cardiol. 1999 Apr;33(5):1231-7.

Nitric oxide inhibits capacitative cation influx in human platelets by promoting sarcoplasmic/endoplasmic reticulum Ca2+-ATPase-dependent refilling of Ca2+ stores.
Trepakova ES, Cohen RA, Bolotina VM.
Circ Res. 1999 Feb 5;84(2):201-9.

Calcium pump overexpression and myocardial function. Implications for gene therapy of myocardial failure.
Hasenfuss G.
Circ Res. 1998 Nov 2;83(9):966-8. No abstract available.

Atrial Fibrillation (AFib)

  • AFib, the most common type of heart arrhythmia, occurs when the heart beats out of rhythm, and it can lead to increased risk of heart attack and stroke. Reduced Ca²⁺ATPase in the heart is associated with Afib, which can contribute to the development of heart failure.

Atrial fibrillation complicated by heart failure induces distinct remodeling of calcium cycling proteins.
Lugenbiel P, Wenz F, Govorov K, Schweizer PA, Katus HA, Thomas D.
PLoS One. 2015 Mar 16;10(3):e0116395. doi: 10.1371/journal.pone.0116395. eCollection 2015.

Irregular rhythm adversely influences calcium handling in ventricular myocardium: implications for the interaction between heart failure and atrial fibrillation.
Ling LH, Khammy O, Byrne M, Amirahmadi F, Foster A, Li G, Zhang L, dos Remedios C, Chen C, Kaye DM.
Circ Heart Fail. 2012 Nov;5(6):786-93. doi: 10.1161/CIRCHEARTFAILURE.112.968321. Epub 2012 Sep 26.

Blood Clots

  • Blood clots typically occur when you have a cut, the clumping of the blood helps to reduce blood loss. This is called platelet aggregation. However, excessive sustained platelet aggregation can significantly increase your risk of heart attack and stroke. Ca²⁺ATPase, through its stimulation by nitric oxide — a substance the body releases in response to platelet aggregation — is the primary mechanism through which platelet aggregation is reduced and the likelihood of blood clots goes down.

Modulation of vascular sarco/endoplasmic reticulum calcium ATPase in cardiovascular pathophysiology.
Adachi T.
Adv Pharmacol. 2010;59:165-95. doi: 10.1016/S1054-3589(10)59006-9. Review.

The plasma membrane calcium ATPase modulates calcium homeostasis, intracellular signaling events and function in platelets.
Jones S, Solomon A, Sanz-Rosa D, Moore C, Holbrook L, Cartwright EJ, Neyses L, Emerson M.
J Thromb Haemost. 2010 Dec;8(12):2766-74. doi: 10.1111/j.1538-7836.2010.04076.x.

Effects of plasma membrane Ca(2+) -ATPase tyrosine phosphorylation on human platelet function.
Bozulic LD, Malik MT, Dean WL.
J Thromb Haemost. 2007 May;5(5):1041-6.

Brain Function

  • Adequate Ca²⁺ATPase is necessary in the brain to prevent excessive intracellular calcium levels. Excessive intracellular calcium levels can have a detrimental effect on many brain processes.

Read more on why calcium homeostasis is essential for the brain on my blog: https://www.brundebroady.com/calcium-regulation-and-the-aging-brain/

Inhibition of PMCA activity by tau as a function of aging and Alzheimer’s neuropathology.
Berrocal M, Corbacho I, Vázquez-Hernández M, Ávila J, Sepúlveda MR, Mata AM.
Biochim Biophys Acta. 2015 Jul;1852(7):1465-76. doi: 10.1016/j.bbadis.2015.04.007. Epub 2015 Apr 16.

Impairment of the activity of the plasma membrane Ca²⁺-ATPase in Alzheimer’s disease.
Mata AM, Berrocal M, Sepúlveda MR.
Biochem Soc Trans. 2011 Jun;39(3):819-22. doi: 10.1042/BST0390819. Review.

Plasma membrane Ca-ATPases: Targets of oxidative stress in brain aging and neurodegeneration.
Zaidi A.
World J Biol Chem. 2010 Sep 26;1(9):271-80. doi: 10.4331/wjbc.v1.i9.271.

Oxidative Stress and the Aging Brain: From Theory to Prevention.
Gemma C, Vila J, Bachstetter A, Bickford PC.
In: Riddle DR, editor. Brain Aging: Models, Methods, and Mechanisms. Boca Raton (FL): CRC Press/Taylor & Francis; 2007. Chapter 15.

Microsomal Ca2+ flux modulation as an indicator of heavy metal toxicity.
Pentyala S, Ruggeri J, Veerraju A, Yu Z, Bhatia A, Desaiah D, Vig P.
Indian J Exp Biol. 2010 Jul;48(7):737-43.

Calcium in the initiation, progression and as an effector of Alzheimer’s disease pathology.
Green KN.
J Cell Mol Med. 2009 Sep;13(9A):2787-99. doi: 10.1111/j.1582-4934.2009.00861.x. Epub 2009 Jul 24. Review.

Altered Ca2+ dependence of synaptosomal plasma membrane Ca2+-ATPase in human brain affected by Alzheimer’s disease.
Berrocal M, Marcos D, Sepúlveda MR, Pérez M, Avila J, Mata AM.
FASEB J. 2009 Jun;23(6):1826-34. doi: 10.1096/fj.08-121459. Epub 2009 Jan 14.

Neuronal ageing in long-term cultures: alterations of Ca2+ homeostasis.
Toescu EC, Verkhratsky A.
Neuroreport. 2000 Nov 27;11(17):3725-9.

Effects of reactive oxygen species on brain synaptic plasma membrane Ca(2+)-ATPase.
Zaidi A, Michaelis ML.
Free Radic Biol Med. 1999 Oct;27(7-8):810-21.

Age-related decrease in brain synaptic membrane Ca2+-ATPase in F344/BNF1 rats.
Zaidi A, Gao J, Squier TC, Michaelis ML.
Neurobiol Aging. 1998 Sep-Oct;19(5):487-95.

Amyloid beta-peptide impairs ion-motive ATPase activities: evidence for a role in loss of neuronal Ca2+ homeostasis and cell death.
Mark RJ, Hensley K, Butterfield DA, Mattson MP.
J Neurosci. 1995 Sep;15(9):6239-49.

Age-dependent changes in calcium currents and calcium homeostasis in mammalian neurons.
Verkhratsky A, Shmigol A, Kirischuk S, Pronchuk N, Kostyuk P.
Ann N Y Acad Sci. 1994 Dec 15;747:365-81. Review. No abstract available.

Regulation of calcium levels in brain tissue from adult and aged rats.
Michaelis ML, Foster CT, Jayawickreme C.
Mech Ageing Dev. 1992 Mar 1;62(3):291-306.


  • When Ca²⁺ATPase is reduced, mast cells release inflammatory substances. The substances released by mast cells are associated with numerous inflammatory conditions, including irritable bowel, arthritis, and other chronic conditions, including diabetes and cardiovascular disease.

Cardiac inflammation involving in PKCε or ERK1/2-activated NF-κB signalling pathway in mice following exposure to titanium dioxide nanoparticles.
Yu X, Hong F, Zhang YQ.
J Hazard Mater. 2016 Aug 5;313:68-77. doi: 10.1016/j.jhazmat.2016.03.088. Epub 2016 Mar 31.

Nitric oxide stress and activation of AMP-activated protein kinase impair β-cell sarcoendoplasmic reticulum calcium ATPase 2b activity and protein stability.
Tong X, Kono T, Evans-Molina C.
Cell Death Dis. 2015 Jun 18;6:e1790. doi: 10.1038/cddis.2015.154.

TNF-α down-regulates sarcoplasmic reticulum Ca²⁺ ATPase expression and leads to left ventricular diastolic dysfunction through binding of NF-κB to promoter response element.
Tsai CT, Wu CK, Lee JK, Chang SN, Kuo YM, Wang YC, Lai LP, Chiang FT, Hwang JJ, Lin JL.
Cardiovasc Res. 2015 Mar 1;105(3):318-29. doi: 10.1093/cvr/cvv008.

Plasma levels of tumor necrosis factor-α and interleukin-6 are associated with diastolic heart failure through downregulation of sarcoplasmic reticulum Ca2+ ATPase.
Wu CK, Lee JK, Chiang FT, Yang CH, Huang SW, Hwang JJ, Lin JL, Tseng CD, Chen JJ, Tsai CT.
Crit Care Med. 2011 May;39(5):984-92. doi: 10.1097/CCM.0b013e31820a91b9.

Evidence that low-grade systemic inflammation can induce islet dysfunction as measured by impaired calcium handling.
Dula SB, Jecmenica M, Wu R, Jahanshahi P, Verrilli GM, Carter JD, Brayman KL, Nunemaker CS.
Cell Calcium. 2010 Aug-Sep;48(2-3):133-42. doi: 10.1016/j.ceca.2010.07.007. Epub 2010 Aug 25.

Effect of proinflammatory cytokines on regulation of sarcoplasmic reticulum Ca2+ reuptake in human airway smooth muscle.
Sathish V, Thompson MA, Bailey JP, Pabelick CM, Prakash YS, Sieck GC.
Am J Physiol Lung Cell Mol Physiol. 2009 Jul;297(1):L26-34. doi: 10.1152/ajplung.00026.2009. Epub 2009 Apr 24.

Cytokines downregulate the sarcoendoplasmic reticulum pump Ca2+ ATPase 2b and deplete endoplasmic reticulum Ca2+, leading to induction of endoplasmic reticulum stress in pancreatic beta-cells.
Cardozo AK, Ortis F, Storling J, Feng YM, Rasschaert J, Tonnesen M, Van Eylen F, Mandrup-Poulsen T, Herchuelz A, Eizirik DL.
Diabetes. 2005 Feb;54(2):452-61.

Effect of Ca(2+) ATPase inhibitors on MCP-1 release from bone marrow-derived mast cells and the involvement of p38 MAP kinase activation.
Teshima R, Onose J, Okunuki H, Sawada J.
Int Arch Allergy Immunol. 2000 Jan;121(1):34-43.

Ca2+-ATPase inhibitor induces IL-4 and MCP-1 production in RBL-2H3 cells.
Onose J, Teshima R, Sawada J.
Immunol Lett. 1998 Nov;64(1):17-22.

Ca2+-ATPase inhibitors and PKC activation synergistically stimulate TNF-alpha production in RBL-2H3 cells.
Teshima R, Onose J, Ikebuchi H, Sawada J.
Inflamm Res. 1998 Aug;47(8):328-33.

Effects of 2,5-di(tert-butyl)-1,4-hydroquinone on intracellular free Ca2+ levels and histamine secretion in RBL-2H3 cells.
Kitajima S, Momma J, Tsuda M, Kurokawa Y, Teshima R, Sawada J.
Inflamm Res. 1995 Aug;44(8):335-9.

The Toxins

Learn about the everyday toxins and their negative effect on Ca²⁺ATPase.


Studies show that benzo(a)pyrenes have a negative impact on Ca²⁺ATPase in the brain, red blood cells, and lungs. Benzo(a)pyrenes have...


Bisphenol (BPA)

Studies have shown that bisphenol has a negative effect on Ca²⁺ATPase in the brain, skeletal muscle, and testes.


High Blood Sugar

Studies show that high blood sugar has a negative impact on Ca²⁺ATPase levels in the heart, brain, arteries, kidneys, and...



Studies show that organophosphate pesticides inhibit Ca²⁺ATPase in the brain, skeletal muscle, lungs, and red blood cells; Pyrethroids inhibit Ca²⁺ATPase...


Polychlorinated Bisphenols (PCBs)

Studies show that polychlorinated bisphenols have a negative impact on Ca²⁺ATPase in the brain.


Potassium Bromate

Studies show that potassium bromate has a negative impact on Ca²⁺ATPase in the liver, kidneys, and possibly in the brain.


Preservatives BHT, BHA, and TBHQ

Studies show that BHT has a negative effect on Ca²⁺ATPase in the brain, skeletal muscles, testes, and mast cells; BHA...


Red Dye #3