Opioid Inhibition of Ca<sup>2+</sup> Channel Subtypes in Bovine Chromaffin Cells: Selectivity of Action and Voltage‐dependence

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<jats:title>Abstract</jats:title><jats:p>Bovine chromaffin cells possess a mixture of high‐voltage‐activated Ca<jats:sup>2+</jats:sup> channel subtypes: L‐type, dihydropyridine‐sensitive channels, and N‐, P‐ and Q‐types, ω‐conotoxin MVIIC‐sensitive channels. In these cells, we studied the reversible, naloxone‐antagonized inhibition of Ba<jats:sup>2+</jats:sup> currents by the opioid agonist met‐enkephalin (IC<jats:sub>50</jats:sub>= 272 nM). This inhibition could be resolved into a voltage‐dependent and a voltage‐independent component. The first was revealed by its slow Ba<jats:sup>2+</jats:sup> current activation kinetics at 0 mV and by the current facilitation induced by short prepulses to +90 mV. The second was estimated as the residual inhibition persisting after the facilitation protocol. The two inhibitory components varied markedly from cell to cell and each contributed to about half of the total inhibition. Replacement of internal GTP by GDP‐β‐S or cell pretreatment with pertussis toxin completely abolished the voltage‐dependent inhibition by opioids, partially preserving the voltage‐independent component. The opioid‐induced inhibition was not selective for any Ca<jats:sup>2+</jats:sup> channel subtype, being not prevented after the addition of specific Ca<jats:sup>2+</jats:sup> channel antagonists. However, when separately analyzing the contribution of each channel type to the voltage‐dependent and voltage‐independent modulation, a clear‐cut distinction could be achieved. The voltage‐independent inhibition was effective on all Ca<jats:sup>2+</jats:sup> channel subtypes but predominantly on L‐type Ca<jats:sup>2+</jats:sup> channels. The voltage‐dependent process was abolished by ω‐conotoxin‐MVIIC, but unaffected by nifedipine, and was thus sharply restricted to non‐L‐type channels (N‐, P‐ and Q‐types). Our data suggest a functionally distinct opioid receptor‐mediated modulation of L‐ and non‐L‐type channels, i.e. of the two channel classes sharing major control of catecholamine secretion from bovine chromaffin cells.</jats:p>

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