Origin of the Background Sodium Current and Effects of Sodium Removal in Cultured Embryonic Cardiac

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/cm2 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/cm2. 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 block