The Sodium‐Calcium Ion Membrane Exchanger: Physiologic Significance and Pharmacologic Implications

Abstract

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.

Ischaemic preconditioning reduces myocardial calcium overload in coronary‐occluded pig hearts shown by continuous in vivo assessment using microdialysis

“…Myocardial ischaemia on a cellular level rapidly leads to a shortage of energy supply in form of ATP and creatine phosphate. Potassium ion outflux and sodium ion influx concomitantly with water influx leads in turn to a net calcium ion influx, resulting in calcium ion overload and oedema (Haworth et al, 1987;Satoh et al, 1995;Haworth & Goknur, 1996;Yashar et al, 1998). At some point during an ischaemic period, the myocardial glycogen stores can no longer be exploited, and then this energy pathway contributes no further (Å berg et al, 2010).…”

Molecular Control of Cardiac Sodium Homeostasis in Health and Disease

“…The third transporter is the NCX1. NCX1 is expected to play a major role in the Ca loading that leads to cardiac myocyte damage in ischemia 40 . Several studies report beneficial effects of inhibiting NCX1 in models of cardiac ischemia 9,10,37,38,51–53 .…”

Effects of ion channel modulators in the influx and efflux of Tc-99m-MIBI

“…I•i6,I7 Our previous studies pointed out that Tc99m-MIBI behaves like Na+ and utilizes Na+/H+ antiport during its uptake, and its uptake is related to the intracellular Na+ concentration.9•18 If Tc-99m-MIBI behaves like Na+ and utilizes Na/H+ antiport, it may involve the Na/ Ca" exchange pathway to maintain the equilibrium which is one of the pathways for maintaining the intracellular Na+ and Ca++ concentrations. 19 But it is not yet determined whether Na+/Cam exchange pathway is involved during the influx or efflux of Tc-99m-MIBI in the cells.…”