The sodium-calcium ion membrane exchanger: physiologic significance and pharmacologic implications.
The Na(+)-Ca2+ exchanger is a non-ATP-dependent protein that, under steady-state conditions, extrudes Ca2+ from the interior of the cell into the extracellular space via facilitated transport. The activity of the exchanger seems to be reduced in myocardial ischemia, leading to increased intracellular Ca2+ in the ischemic heart, which can result in arrhythmia, myocardial stunning, and necrosis. In contrast, congestive heart failure and myocardial hypertrophy are associated with increased exchanger activity and a decreased inotropic state. Pharmacologic agents are being developed to modulate sodium ion levels in the cell, which could enhance or reduce sodium-calcium exchange as needed in various pathophysiologic states. At this time there are no available drugs that act specifically on the Na(+)-Ca2+ exchanger itself. The exchanger has been cloned, and inhibitory peptides of the exchanger may soon be available for possible use in treatment of congestive heart failure.
Yashar
P R
PR
Department of Medicine, Cedars-Sinai Medical Center, UCLA School of Medicine, USA.
Fransua
M
M
Frishman
W H
WH
D001384:Azetidines / Q000494:pharmacology / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D011487:Protein Conformation; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D001384:Azetidines; D002316:Cardiotonic Agents; D010879:Piperazines; D019831:Sodium-Calcium Exchanger; C071117:BDF 9148; C046261:DPI 201-106; D012964:Sodium; D002118:Calcium