Low pO2 selectively inhibits K channel activity in chemoreceptor cells of the mammalian carotid body

Abstract

The hypothesis that changes in environmental 02 tension (pOi) could affect the ionic conductances of dissociated type I cells of the carotid body was tested. Cells were subjected to whole-cell patch clamp and ionic currents were recorded in a control solution with normal pO 2 (pO~ = 150 mmHg) and 3-5 min after exposure to the same solution with a lower pO,. Na and Ca currents were unaffected by lowering pO, to 10 mmHg, however, in all cells studied (n = 42) exposure to hypoxia produced a reversible reduction of the K current. In 14 cells exposed to a pO 2 of 10 mmHg peak K current amplitude decreased to 35 +_ 8% of the control value. The effect of low pO2 was independent of the internal Ca 2+ concentration and was observed in the absence of internal exogenous nucleotides. Inhibition of K channel activity by hypoxia is a graded phenomenon and in the range between 70 and 120 mmHg, which includes normal pO, values in arterial blood, it is directly correlated with pO 2 levels. Low pO2 appeared to slow down the activation time course of the K current but deactivation kinetics seemed to be unaltered. Type I cells subjected to current clamp generate large Na- and Cadependent action potentials repetitively. Exposure to low pO~ produces a 4-10 mV increase in the action potential amplitude and a faster depolarization rate of pacemaker potentials, which leads to an increase in the firing frequency. Repolarization rate of individual action potentials is, however, unaffected, or slightly increased. The selective inhibition of K channel activity by low pO, is a phenomenon without precedents in the literature that explains the chemoreceptive properties of type I cells. The nature of the interaction of molecular O, with the K channel protein is unknown, however, it is argued that a hemoglobin-like O, sensor, perhaps coupled to a G protein, could be involved.