The kinetics of recovery and development of potassium channel inactivation in perfused squid (Loligo pealei) giant axons.

K+ currents were studied at a normal (‐69 mV) and at a depolarized (‐49 mV) membrane potential in voltage‐clamped squid giant axons perfused with 350 mM‐K+ and bathed in K+‐free artificial sea water containing tetrodotoxin to block the Na+ channels. Steady‐state and instantaneous K+ currents were reduced by over 50% at corresponding voltages at the depolarized membrane potential. Instantaneous chord conductance‐voltage curves showed that the depolarized membrane potential caused a uniform reduction of K+ conductance across the voltage range under study. The driving force for K+ ions was comparable at both membrane potentials when a short (2 ms) pre‐pulse was used to open the K+ channels. When a longer (7.5 ms) pre‐pulse was used, the driving force was actually larger at the depolarized membrane potential. The depolarized membrane potential did drive some K+ ions into the periaxonal space. The amount of K+ ions driven into the periaxonal space was estimated by two independent methods, with similar results. The resulting increase of K+ ions in the periaxonal space (10 mM) was about 40 times too small to account for the large reduction in currents in terms of a reduced driving force for K+ ions. The kinetics of recovery and development of inactivation were monitored by repeatedly applying a 7.5 ms test pulse followed by a long conditioning potential. Both recovery and development of inactivation, from the depolarized membrane potential, were described by the sum of two exponential terms plus a constant. The time constant‐voltage curves for both phases of inactivation peaked at about ‐54 mV at 10 degrees C. The time constant of the slow phase of inactivation at ‐54 mV was about 12.4 s, while the corresponding time constant for the fast phase was about 2.3 s. The slow relaxation had an apparent plateau of about 11 s at more depolarized membrane potentials. Recovery from inactivation was rapid at hyperpolarized membrane potentials. The steady‐state inactivation curve of the K+ channel was incomplete in the depolarizing region; and apparent plateau was reached with about 75% of the K+ current inactivated. The temperature sensitivity of both phases of inactivation corresponded to a Q10 of about 3. Elevated external concentrations of K+ ions did not block either phase of the inactivation process, although the kinetics of recovery from inactivation were slightly faster under these conditions.(ABSTRACT TRUNCATED AT 400 WORDS)