The differential effects of tetraethylammonium and zinc ions on the resting conductance of frog skeletal muscle.

1. The effects of tetraethylammonium (TEA) and zinc ions on the resting conductance of frog muscle were examined using a method which permitted control of the membrane potential near the end of a muscle fibre and measurement of an approximation of the membrane current.2. TEA reduced the amplitude of the inactivating inward current obtained on hyperpolarizing, both when this was measured as initial current [I(m)(0)] less the estimated chloride current and as [I(m)(0) - I(m)(infinity)]. 115 mM-TEA reduced the amplitude of [I(m)(0) - I(m)(infinity)] by about 85%.3. TEA had little effect on the time constant with which the inward potassium currents inactivated. This finding appeared to be in conflict with the view that the inactivation is due to depletion of potassium from the T-system, though the results in standard Ringer were in good agreement with such an hypothesis.4. In the standard chloride Ringer, the resting membrane resistance was 3530 Omega cm(2). 115 mM-TEA increased this 1.6 times to 5580 Omega cm(2).5. The effect of TEA on voltage-current relations obtained in high K(2)SO(4) solutions was also examined. With large pulses, the voltage-current relations in TEA and control solutions tended to become linear. This linear part could be extrapolated and subtracted from the voltage-current relation.6. TEA, at a concentration of 150 mM, reversibly reduced by 88% the amplitude of the currents obtained during both depolarizing and hyperpolarizing pulses; this figure was obtained after subtraction of the linear part of the relation, which was itself unaffected by TEA and which represented a resistance of 5600 Omega cm(2).7. The reductions in the inactivating potassium current and in the current flowing through the inwardly rectifying potassium channel in high K(2)SO(4) solutions fit, fairly closely, a concentration-effect relation for TEA with a dissociation constant of 20 x 10(-3)M.8. Also investigated were the slow time-dependent changes in membrane potential occurring when [K](o) is altered from 2.5 to 10 mM at constant chloride (120 mM). The findings were consistent with the view that TEA reduced the potassium conductance without much effect on the chloride conductance. In particular, when muscles equilibrated for 1 hr in 10 mM-K Ringer were returned to 2.5 mM-K, the initial rate of repolarization was reduced, even though the driving force on K was slightly larger than in the control experiment.9. Zinc ions appeared to be without effect either on the amplitude of the inactivating potassium current obtained when square hyperpolarizing pulses were applied to the fibre membrane, or on its time constant.10. In standard Tris-buffered Ringer, the membrane resistance was 3350 Omega cm(2). Zinc Ringer (2.5 mM) increased this rather more than twice to 6830 Omega cm(2).11. It is concluded that the two agents, TEA(+) and Zn(2+), which both reduce delayed potassium currents in muscle, act in different ways on the resting conductance of frog muscle.