Acetaldehyde-ethanol interactions on calcium-activated potassium (BK) channels in pituitary tumor (GH3) cells

BACKGROUND In the central nervous system ethanol (EtOH) is metabolized to acetaldehyde (ACA) primarily by the oxidative enzyme catalase. Evidence suggests that ACA is responsible for at least some of the effects on the brain that have been attributed to EtOH. Various types of ion channels which are involved in electrical signaling are targets of EtOH like maxi calcium-activated potassium (BK) channels. BK channels exhibit various functions like action potential repolarization, blood pressure regulation, hormone secretion, or transmitter release. In most neuronal and neuroendocrine preparations at physiological intracellular calcium levels, EtOH increases BK channel activity. The simultaneous presence of ACA and EtOH reflects the physiological situation after drinking and may result in synergistic as well as antagonistic actions compared to a single application of either drug. The action of ACA on electrical activity has yet not been fully established. METHODS GH3 pituitary tumor cells were used for outside-out and inside-out patch-clamp recordings of BK activity in excised patches. Unitary current amplitude, open probability and channel mean open time of BK channels were measured. RESULTS Extracellular EtOH raised BK channel activity. In the presence of intracellular ACA this increment of BK activity was suppressed in a dose- as well as calcium-dependent manner. Mean channel open time was significantly reduced by internal ACA, whereas BK channel amplitudes were not affected. The EtOH counteracting effect of ACA was found to depend on succession of application. EtOH was prevented from activating BK channels by pre-exposure of membrane patches to ACA. In contrast BK activation by a hypotonic solution was not affected by internal ACA. CONCLUSIONS Our data suggest an inhibitory impact of ACA on BK activation by EtOH. ACA appears to interact specifically with EtOH at BK channels since intracellular ACA had no effect when BK channels were activated by hypotonicity.