Effect of BHT 920 on calcium-activated K+ channels in renal epithelioid MDCK cells.
In Madin Darby canine kidney (MDCK) cells, epinephrine has been shown to increase intracellular calcium, activate calcium-dependent K+ channels and hyperpolarize the cell membrane. The present study has been performed to test for the possible involvement of alpha 2-adrenergic receptors. To this end, the effects of alpha 2-adrenoceptor agonist BHT 920 have been studied on cell membrane potential, ion channel activity and intracellular calcium: Similar to epinephrine, BHT 920 hyperpolarizes the cell membrane, increases intracellular calcium and activates inwardly rectifying K+ channels (single channel slope conductances 30-80 pS). Half-maximal hyperpolarization is achieved at concentrations between 10 and 100 nmol/l. The hyperpolarizing effect of BHT 920 is abolished in the presence of alpha 2-adrenoceptor antagonist yohimbine (100 nmol/l) but not in the presence of alpha 1-adrenoceptor antagonist prazosin (100 nmol/l). At extracellular calcium activity below 100 nmol/l BHT 920 still leads to a transient hyperpolarization of the cell membrane but, in contrast to epinephrine, is unable to significantly increase intracellular calcium or significantly activate the calcium-sensitive K+ channels. The observations indicate that stimulation of alpha 2-receptors participates in the epinephrine-induced increase of intracellular calcium, channel activation and hyperpolarization.
Weiss
H
H
Institute for Physiology, University of Innsbruck, Austria.
Friedrich
F
F
Paulmichl
M
M
Wöll
E
E
Lang
F
F
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D002460:Cell Line; D003600:Cytosol / Q000737:chemistry / Q000187:drug effects; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects; D007668:Kidney; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D001381:Azepines; D015221:Potassium Channels; C024763:talipexole; D002118:Calcium; D004837:Epinephrine