Plasma membrane calcium pumps in smooth muscle: from fictional molecules to novel inhibitors.
Plasma membrane Ca2+ pumps (PMCA pumps) are Ca2+-Mg2+ ATPases that expel Ca2+ from the cytosol to extracellular space and are pivotal to cell survival and function. PMCA pumps are encoded by the genes PMCA1, -2, -3, and -4. Alternative splicing results in a large number of isoforms that differ in their kinetics and activation by calmodulin and protein kinases A and C. Expression by 4 genes and a multifactorial regulation provide redundancy to allow for animal survival despite genetic defects. Heterozygous mice with ablation of any of the PMCA genes survive and only the homozygous mice with PMCA1 ablation are embryolethal. Some PMCA isoforms may also be involved in other cell functions. Biochemical and biophysical studies of PMCA pumps have been limited by their low levels of expression. Delineation of the exact physiological roles of PMCA pumps has been difficult since most cells also express sarco/endoplasmic reticulum Ca2+ pumps and a Na+-Ca2+-exchanger, both of which can lower cytosolic Ca2+. A major limitation in the field has been the lack of specific inhibitors of PMCA pumps. More recently, a class of inhibitors named caloxins have emerged, and these may aid in delineating the roles of PMCA pumps.
Pande
Jyoti
J
Department of Medicine, McMaster University, Hamilton, ON, Canada.
Grover
Ashok K
AK
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D009130:Muscle, Smooth / Q000201:enzymology*; D010455:Peptides / Q000378:metabolism; D053499:Plasma Membrane Calcium-Transporting ATPases; D012519:Sarcoplasmic Reticulum / Q000201:enzymology
C506952:ATP2B1 protein, human; D027682:Cation Transport Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C501980:caloxin 1A1; C423122:caloxin 2A1; C501841:caloxin 3A1; D053499:Plasma Membrane Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases