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The Journal of General Physiology, Vol 100, 427-455, Copyright © 1992 by The Rockefeller University Press
ARTICLES |
MD Ganfornina and J Lopez-Barneo
Departamento de Fisiologia y Biofisica, Facultad de Medicina, Universidad de Sevilla, Spain.
We have studied the kinetic properties of the O2-sensitive K+ channels (KO2 channels) of dissociated glomus cells from rabbit carotid bodies exposed to variable O2 tension (PO2). Experiments were done using single-channel and whole-cell recording techniques. The major gating properties of KO2 channels in excised membrane patches can be explained by a minimal kinetic scheme that includes several closed states (C0 to C4), an open state (O), and two inactivated states (I0 and I1). At negative membrane potentials most channels are distributed between the left-most closed states (C0 and C1), but membrane depolarization displaces the equilibrium toward the open state. After opening, channels undergo reversible transitions to a short-living closed state (C4). These transitions configure a burst, which terminates by channels either returning to a closed state in the activation pathway (C3) or entering a reversible inactivated conformation (I0). Burst duration increases with membrane depolarization. During a maintained depolarization, KO2 channels make several bursts before ending at a nonreversible, absorbing, inactivated state (I1). On moderate depolarizations, KO2 channels inactivate very often from a closed state. Exposure to low PO2 reversibly induces an increase in the first latency, a decrease in the number of bursts per trace, and a higher occurrence of closed-state inactivation. The open state and the transitions to adjacent closed or inactivated states seem to be unaltered by hypoxia. Thus, at low PO2 the number of channels that open in response to a depolarization decreases, and those channels that follow the activation pathway open more slowly and inactivate faster. At the macroscopic level, these changes are paralleled by a reduction in the peak current amplitude, slowing down of the activation kinetics, and acceleration of the inactivation time course. The effects of low PO2 can be explained by assuming that under this condition the closed state C0 is stabilized and the transitions to the absorbing inactivated state I1 are favored. The fact that hypoxia modifies kinetically defined conformational states of the channels suggests that O2 levels determine the structure of specific domains of the KO2 channel molecule. These results help to understand the molecular mechanisms underlying the enhancement of the excitability of glomus cells in response to hypoxia.
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