1. The pH- and voltage-dependent Cl- conductance in frog muscle may be related to the chloride equilibrium potential, VCl,eq, rather than to the absolute membrane potential, Vm. This hypothesis was tested in thin depolarized frog muscle fibre bundles by investigating the influence of pH on 36Cl- efflux during Cl- net efflux upon removal of external Cl-, which offers a state far from Cl- equilibrium by changing VCl,eq instead of Vm. 2. Upon the change from Cl- equilibrium at 20 mM-Clo- to Cl- net efflux at zero [Cl-]o, Vm changed only approximately 10 mV, but the 36Cl- efflux rate increased about three times at pH 5.5 and decreased to less than one tenth of the equilibrium efflux rate at pH 9.8. The switch between 'acid' and 'alkaline' responses occurs at a pH between 6.4 ('acid response') and 7.2 ('alkaline response'). 3. Changing pH between 5.5 and 9.8 during Cl- net efflux showed an increase of 36Cl- net flux rate upon acidification and a decrease upon alkalinization. The reactions are opposite to those seen by pH shifts at chloride equilibrium. 4. The changes of net flux rate coefficients upon changes of pH were transient, especially the activation at low pH that relaxed significantly during about 10 min. 5. The results are consistent with the notion that the state of the gCl mechanism in frog muscle is related to (Vm-VCl,eq) rather than to the absolute potential alone.
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