Calcium channel currents in bovine adrenal chromaffin cells and their modulation by anaesthetic agents.
1. The calcium channel currents of bovine adrenal chromaffin cells were characterized using a variety of voltage pulse protocols and selective channel blockers before examination of their modulation by anaesthetic agents. 2. All the anaesthetics studied (halothane, methoxyflurane, etomidate and methohexitone) inhibited the calcium channel currents in a concentration-dependent manner and increased the rate of current decay. 3. The anaesthetics did not shift the current-voltage relation nor did they change the voltage for half-maximal channel activation derived from analysis of the voltage dependence of the tail currents. None of the anaesthetics appeared to alter the time constant of tail current decay. 4. To complement earlier studies of the inhibitory actions of anaesthetics on K(+)-evoked catecholamine secretion and the associated Ca2+ uptake, the IC50 values for etomidate and methohexitone were determined using a biochemical assay. The IC50 values for anaesthetic inhibition of calcium channel currents corresponded closely with those for inhibition of K(+)-evoked calcium uptake and catecholamine secretion. 5. The inhibitory effect of the volatile anaesthetics and etomidate is best explained by dual action: a reduction in the probability of channel opening coupled with an increase in the rate of channel inactivation. Methohexitone appeared to inhibit the currents by a use-dependent slow block.
Charlesworth
P
P
Department of Physiology, Royal Free Hospital School of Medicine, London, UK.
Pocock
G
G
Richards
C D
CD
D000313:Adrenal Medulla / Q000166:cytology*; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D004594:Electrophysiology; D005045:Etomidate / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D008723:Methohexital / Q000494:pharmacology; D008733:Methoxyflurane / Q000494:pharmacology; D011188:Potassium / Q000502:physiology
D000777:Anesthetics; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002395:Catecholamines; D008733:Methoxyflurane; D008723:Methohexital; D011188:Potassium; D002118:Calcium; D006221:Halothane; D005045:Etomidate