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 -90mV induced fast-activating, fast-inactivating inward currents (fast currents), which were followed by slowly-inactivating inward currents (slow currents). Using a nominally Ca2+-free bath solution, depolariz ation steps up to +20mV induced only the fast currents, and depolariza tion steps to over +30 mV evoked outward currents. The fast current wa s inhibited by tetrodotoxin (TTX) or by removal of external Na+, there by 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 th e 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 Ni2and Cd2+ was more potent than Ni2+ or Mn2+ as a Na+ channel blocker. P lots of peak current amplitude, as a function of Cd2+ concentration, s howed that one Cd ion was required to block one Na+ channel (K-D: 55.7 mu M). Thus, properties of the Na+ channel found in this smooth muscl e cells are similar to those in vertebrate cardiac cells, in that the channel is relatively resistant to TTX and is sensitive to Cd2