Substates of cardiac sodium channels are due to both decrease in conductance and changes in selectivity.

Currents through DPI 201-106 modified single cardiac sodium channels in guinea pig ventricular cells were measured using the patch clamp technique in the cell-free configuration to control the sodium concentrations on both sides of the patch membrane. Current-voltage relationships of the single channels were obtained by application of linear voltage ramps from -140 to 100 mV. With 10 mmol/l Na+ at the inner surface of the patch, openings of sodium channels with conductances of 17 pS (selectivity ratios PK/PNa = 0.083 and PK/PNa = 0.58) and 12 pS (selectivity ratios PK/PNa = 0.084 and PK/PNa = 1.832) were obtained. With 30 mmol/l internal sodium, conductances of 20, 10, and 7 pS and selectivity ratios of 0.084, 0.386, and 0.543, respectively, could be measured. It is concluded that substates of sodium channel currents are due to changes in single channel conductance as well as in selectivity, or to changes of both independently of each other which accounts for the variability of conductance levels of cardiac Na channels.