Blockade of sodium channels by divalent cations in rat gastric smooth muscle.
Using the whole-cell clamp method, the Na+ channel currents in smooth muscle cells of the rat stomach fundus were studied. After blocking K+ channel currents, step depolarizations from the holding potential of -90 mV induced fast-activating, fast-inactivating inward currents (fast currents), which were followed by slowly-inactivating inward currents (slow currents). Using a nominally Ca(2+)-free bath solution, depolarization steps up to +20 mV induced only the fast currents, and depolarization steps to over +30 mV evoked outward currents. The fast current was inhibited by tetrodotoxin (TTX) or by removal of external Na+, thereby indicating that this was a Na+ channel current. The outward current was inhibited by nifedipine or by 0.1 mM Ca2+, thus, this current was a Cs+ current passing through Ca2+ channels. In the presence of 5 mM Ni2+, the Na+ current was reduced to about 15% of the control. When the rightward shift in the I-V relations was taken into account, the Na+ current was about 30% of the control. Mn2+ was less potent than Ni2+, and Cd2+ was more potent than Ni2+ or Mn2+, as a Na+ channel blocker. Plots of peak current amplitude, as a function of Cd2+ concentration, showed that one Cd ion was required to block one Na+ channel (KD: 55.7 microM). Thus, properties of the Na+ channel found in this smooth muscle cells are similar to those in vertebrate cardiac cells, in that the channel is relatively resistant to TTX and is sensitive to Cd2+.