Abstract
We have investigated the reduction of steady state sodium channel currents by a monovalent and a divalent guanidinium analogue. The amount of block by the divalent compound at a constant membrane potential was dramatically reduced by an increase in the internal salt concentration. Channel block by the monovalent molecule was a less steep function of salt concentration. These results would be expected if there were negative charges near the sodium pore that produced a local accumulation of the cationic blocking ions. According to this view, the ionic strength dependence of block results from changes in surface potential. The divalent blocker would be expected to be more sensitive to ionic strength owing to its larger valence. Our results can be quantitatively described by a simple ionic double-layer model with an effective surface charge density of about -1 e/250 A2 in the vicinity of the pore.
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