SODIUM CURRENT INHIBITION BY INTERNAL CALCIUM - A COMBINATION OF OPEN-CHANNEL BLOCK AND SURFACE-CHARGE SCREENING

Internal application of millimolar concentrations of calcium to batrac hotoxin (BTX)-activated rat skeletal muscle sodium channels, bathed sy mmetrically in 200 mM NaCl, causes a reduction in apparent single-chan nel amplitude without visibly increasing noise at a bandwidth of 50 Hz . A greater calcium-induced reduction occurred upon removal of externa l sodium ions. Internal calcium acted similarly in high ionic strength solutions (3M NaCl), where surface charges are effectively screened, suggesting that calcium acts, in part, by binding within the pore and occluding the conducting pathway. In low ionic strength solutions (20 mM NaCl), internal addition of N-Methyl-Glucamine (NMG) ions decreased the single channel amplitude consistent with screening of negative su rface charges. An accurate description of the dose dependence of calci um inhibition, using either a simple blocking model, or rate theory ca lculations of ion permeation and block, also required surface charge s creening. Hence, our data support the view that sodium current inhibit ion by internal calcium arises from a combination of both open-channel block and surface charge effects.