Origin of the background sodium current and effects of sodium removal in cultured embryonic cardiac cells.

Abstract

SUMMARY. Cardiac automaticity is partly due to a diastolic sodium current. Possible mediators of this include tetrodotoxin-sensitive "fast" channels, cesium-sensitive time-dependent pacemaker current channels, calcium-gated nonspecific channels, and electrogenic sodium-calcium exchange. We have studied the effects of abrupt sodium removal on membrane current and conductance in voltage-clamped chick embryonic myocadial cell aggregates, in the presence of various sodium flux inhibitors. Total replacement of sodium by lithium, Tris, or tetraethylammonium ions in aggregates clamped in the pacemaker range caused a brief outward current followed by a sustained net inward current. The outward current reached a peak value of 1.1 ± 0.5 /iA/cm 2 at a mean latency of 5.4 ±1.2 sec. (n = 6; V = -70.5 ± 8.9 mV; Tris). Conductance often decreased during the outward current. The inward current developed exponentially (T = 19 ± 5 sec) and reached a steady state value of -1.6 ± 0.4 //A/cm 2 . This current was reversed by depolarization (mean reversal potential = -13 ± 13 mV), and was accompanied by increased conductance and spontaneous mechanical activity. Neither of the sodium-removal currents was affected by 20 ^M tetrodotoxin. Cesium (up to 20 ITIM) had no effect on the late inward current or the mechanical activity, but decreased the early outward current by 80 ± 12%. Manganese (25 mvi), which blocks sodium-calcium exchange, abolished the late inward current and the mechanical activity. Manganese also reduced the early outward current by 27 ± 10%. Manganese and cesium together blocked all the effects of sodium removal. We conclude that removal of extracellular sodium interrupts a cesium-sensitive "background" current, that may be related to the time-dependent pacemaker current, I f . Sodium removal also causes gradual activation of a nonspecific conductance, which can ultimately depolarize the cells, and which may be gated by cytoplasmic calcium. (Circ Res 55: 67-77, 1984)

Effects of sodium‐potassium pump inhibition and low sodium on membrane potential in cultured embryonic chick heart cells.

“…the potential to which Em was hyperpolarizing on exposure to low [Na+]O. This explanation is consistent with the results of Mead & Clusin (1984) who reported a Cs+-sensitive current in cultured chick embryo heart cells on removal of external Na+: they tentatively related this current to if. An alternative explanation for the action of Cs+ could be that it was blocking Na+-Ca2+ exchange.…”

Paradoxical electromechanical effect of lanthanum ions in cardiac muscle cells

“…In digitalis toxicity, spontaneous intracellular calcium release causes a characteristic inward current that is due, at least in part, to calcium-activated inward current channels (13)(14)(15). This mechanism also accounts for the membrane conductance increase that occurs when intracellular calcium is increased by removal of external sodium (16)(17). Another manifestation of intracellular calcium release are the disorganized local contractions that occur in calcium overload or, to a lesser degree, in normal unstimulated myocardium (18)(19)(20)(21)(22).…”

The Dependence of the Strength of Sodium‐depletion Contractures of Isolated Frog Atrial Trabeculae on the Membrane Potential

“…These results can also be interpreted, however, in terms of the activation of a K current by the changes in intracellular [Ca] (Einwachter & Brommundt, 1978;Mead & Clusin, 1984). In cultured chick heart cells, however, the activation of the Na/Ca exchange can drive the membrane potential below the K equilibrium potential, suggesting that this is not due to the activation of a K channel but an electrogenic Na/Ca exchange (Jacob et al 1984).…”

“…The relationship between extracellular Na concentration ([Na]o) and contracture tension and the shift in this relationship produced by raising the [K]o has been interpreted quantitatively in terms of an exchange of Na+ for Ca2+ across In intact preparations of both mammalian and amphibian heart, a number of studies have produced indications of an electrogenic Na/Ca exchange. The evidence for this conclusion was derived from studies of either the sensitivity of the developed tension to membrane potential (Horackova & Vassort, 1979;Bonvallet, Ildefonse, Roche & Rougier, 1981), or the appearance of a membrane current supposed to be due to an activation of the Na/Ca exchange (Goto, Urata & Hyodo, 1981;Jacob, Liu, Murphy & Lieberman, 1984;Mead & Clusin, 1984;Mentrard, Vassort & Fischmeister, 1984;Arlock & Noble, 1985;Hadley, Hume, Kaczorowski, Siegl & Vassilev, 1985;Kimura, Noma & Irisawa, 1986).…”