The influence of the permeant ions thallous and potassium on inward rectification in frog skeletal muscle.

A three-electrode voltage-clamp method was used to investigate the inactivation of Tl currents through the inward rectifier of frog sartorius muscle fibres, and the interaction between the permeant ions Tl+ and K+. In 80 mM-Tl Ringer inward currents inactivated on hyperpolarization along an exponential time course, with time constants that initially increased and then fell with increasing hyperpolarization. Because of the inactivation process steady-state conductances were smaller than instantaneous conductances at all potentials in Tl Ringer. The steady-state conductance increased to a maximum value at around - 100 mV in 80 mM-Tl Ringer, and then fell with increasing hyperpolarization. In K Ringer the steady-state conductance was greater at all potentials than the instantaneous conductance because K currents activate (rather than inactivate) on hyperpolarization. Time constants of Tl inactivation were the same when measured from the decay of current during a single pulse, or from the rate of recovery from inactivation using either a two- or a three-pulse method, indicating that inactivation obeys first-order kinetics. In 80 mM-Tl Ringer steady-state inactivation increased with increasing hyperpolarization, e-fold every 48 mV. This would be consistent with the site at which inactivation occurs experiencing 0.5 of the membrane voltage field. Tl+ was more permeant than K+ through the inward rectifier, the permeability ratio PTl+/PK+ being 1.66. In solutions containing both Tl+ and K+ the membrane showed an anomalous mole-fraction dependence of conductance, the resting potential being more negative, and both instantaneous and steady-state conductances smaller than those recorded in solutions containing only Tl+ or only K+. The reduction in the amplitude of the instantaneous conductance in Tl-K mixtures was voltage-dependent, the block being initially increased and then falling with increasing hyperpolarization. Inward currents also inactivated on hyperpolarization in Tl-K mixtures. The time constants of inactivation, and the extent of inactivation which occurred, became less dependent on membrane potential in these solutions. When K+ is the major permeant ion in solution, Tl+ has a blocking effect on the currents carried by K+, and the degree of block is voltage-dependent. Increasing [Tl]o increased the block at all potentials. The results of our experiments in solutions containing both Tl+ and K+ are discussed in terms of an interaction between these ions within the channel.