OPIOID PEPTIDE MODULATION OF CA2-DEPENDENT K+ AND VOLTAGE-ACTIVATED CA2+ CURRENTS IN BOVINE ADRENAL CHROMAFFIN CELLS()

Opioid peptides are abundantly expressed in the adrenal medulla, and t here is evidence that they may be released presynaptically or as medul lary paracrine agents. To assess the physiological relevance of these observations, we investigated opioid effects on ionic currents from cu ltured bovine adrenal chromaffin cells. Under whole-cell path-clamp co nditions, opioid peptides, acting via a mu-type opioid receptor, stron gly potentiated the large conductance Ca2+-dependent K+ (BK) channel c urrent. Opioids also inhibited voltage-activated Ca2+ currents. Applic ation of opioid peptides to the extracellular face of outside-out patc hes also increased opening activity of single BK channels, suggestive of tight receptor-channel coupling. This potentiating effect on BK cur rent, combined with the inhibition of Ca2+ current, indicates that opi oids may have an inhibitory influence on secretory activity of the adr enal medulla. The widespread distribution of the BK channel class sugg ests that the significance of its modulation by opioids could also ext end beyond the adrenal gland.