Targeting the sarcolemmal calcium pump: a potential novel strategy for the treatment of cardiovascular disease.
Intracellular calcium dynamics play a very important role in mediating contraction and signalling in cardiomyocytes and vascular smooth muscle cells. A number of calcium transporters have been identified that orchestrate a complex process of excitation-contraction coupling and molecular signalling. Despite the variability of the calcium transporters expressed in cardiomyocytes, most calcium channel blockers used therapeutically target the L-type calcium channel and exhibit antihypertensive and/or vasodilating activities. Recently, another calcium pump which is located in the sarcolemma has been shown to mediate cardiac contractility and vascular tone. Interestingly, this sarcolemmal calcium pump (also known as Plasma Membrane Calcium/calmodulin dependent ATPase or PMCA) exerts its function not by altering global calcium concentration, but by mediating signal transduction pathways. This review will discuss recent advances that support the key roles of PMCA as signalling molecule and the potential to target this calcium pump as a novel approach for the treatment of cardiovascular disease.
Oceandy
Delvac
D
Division of Cardiology, University of Manchester, 1.302 Stopford Building, Oxford Road, Manchester, M13 9PT, UK. delvac.oceandy@manchester.ac.uk
Mamas
Mamas A
MA
Neyses
Ludwig
L
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D052139:Intracellular Calcium-Sensing Proteins / Q000502:physiology; D051379:Mice; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000187:drug effects / Q000502:physiology; D012508:Sarcolemma / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D052139:Intracellular Calcium-Sensing Proteins; D053499:Plasma Membrane Calcium-Transporting ATPases