The effect of
hypoxia on small-conductance Ca(2+)-activated K+ current was investigated in a study of adult rat adrenomedullary chromaffin cells (AMCs), which were maintained in short-term culture. The
nystatin-perforated, whole-cell patchclamp technique was used to study the effect of
hypoxia with minimum perturbation of the intracellular milieu. Under voltage-clamp conditions, acute
hypoxia (P(O2) approximately equal to 25 mmHg) suppressed the whole-cell outward currents of more than half the AMCs (24/46). This suppression was eliminated after application of
apamin (400 nM), a selective inhibitor of small-conductance Ca(2+)-activated K+ current (I(SK)(Ca)) (n=5), suggesting that an
apamin-sensitive component of whole-cell currents is suppressed during
hypoxia. In contrast to I(SK)(Ca), Ca2+ current (I(Ca)) (n=10) was not affected by
hypoxia. Finally, under current-clamp conditions,
hypoxia reversibly depolarized the resting membrane potential of adult AMCs (34/40).
Apamin, however, eliminated the
hypoxia-induced depolarization (400 nM) (7/8), suggesting that hypoxic depolarization is related to the suppression of I(SK(Ca). From the above results, we conclude that adult AMCs are sensitive to
hypoxia, and that I(SK)(Ca) contributes to the
hypoxia-induced suppression of whole-cell outward current and depolarization of the resting membrane potential in adult AMCs.