CHLORIDE CURRENT IN TOAD SKELETAL-MUSCLE AND ITS MODIFICATION BY THE HISTIDINE-MODIFYING REAGENT DIETHYLPYROCARBONATE

Cl- currents were measured in short fibres in the toad lumbricalis mus cle with a two-microelectrode voltage clamp. Membrane Cl- conductance increased markedly when external pH was raised. At pH 7 or higher, the Cl- current fell during a hyperpolarizing voltage pulse and the rate of inactivation was directly proportional to the voltage change. The h istidine-modifying reagent diethylpyrocarbonate (DEPC, 1 mM) which car bethoxylates histidil residues in proteins, suppressed the inactivatio n of Cl- currents at pH 7.5. On the other hand, no apparent changes in the kinetics of the currents at pH 5 were seen. NO3- currents, which are independent of the extracellular pH and time, were not affected by DEPC. Our results support the notion that the inactivation of Cl- cur rents at pH 7.5 represents a membrane permeability change and that DEP C interferes with this process. Protonation of histidine groups associ ated with Cl- channels may be the controlling reaction for the pH-depe ndent Cl- response.