The suppression of Ca(2+)‐ and voltage‐dependent outward K+ current during mAChR activation in rat adrenal chromaffin cells.

J. Herrington, C. R. Solaro, A. Neely, C. J. Lingle

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42 Scopus citations

Abstract

1. The mechanism by which muscarine, ionomycin or caffeine results in suppression of Ca(2+)‐ and voltage‐dependent outward current in rat adrenal chromaffin cells was evaluated using both whole‐cell voltage clamp and single channel recording. 2. The whole‐cell current activated following the elevation of the cytosolic calcium concentration ([Ca2+]i) by muscarine inactivates with a time course comparable to that of single Ca(2+)‐ and voltage‐dependent potassium (BK) channels. 3. The whole‐cell inactivating current is pharmacologically similar to BK current. 4. The voltage dependence of inactivation and rate of recovery from inactivation are qualitatively similar for both whole‐cell current and ensemble averages of single BK channels. Furthermore, changes in the rate of whole‐cell current inactivation track expected changes in submembrane [Ca2+]. 5. The suppression of outward current can be accounted for solely by inactivation of BK channels and does not depend on the means by which [Ca2+]i is elevated. 6. Muscarinic acetylcholine receptor (mAChR) activation, changes in holding potential (‐50 to ‐20 mV), and step depolarizations of different amplitude and duration were tested for their ability to elevate [Ca2+]i and thereby regulate the availability of BK current for activation. 7. Following muscarine‐induced elevation of [Ca2+]i at holding potentials positive to ‐40 mV, the availability of BK current for activation was typically reduced by more than 50%. 8. Holding potentials in the range of ‐50 to ‐20 mV produced only slight alterations in the availability of BK current for activation. 9. Step depolarizations that cause maximal rates of Ca2+ influx (0 to +10 mV) must exceed 200 ms to reduce the availability of BK current by approximately 50%. 10. The results show that the muscarine‐induced elevation of [Ca2+]i produces a profound reduction in the availability of BK channels for activation at membrane potentials likely to be physiologically meaningful. Although depolarization‐ induced Ca2+ influx can inactivate BK current, we propose that short duration depolarizations that occur during normal electrical activity will not significantly alter BK channel availability.

Original languageEnglish
Pages (from-to)297-318
Number of pages22
JournalThe Journal of Physiology
Volume485
Issue number2
DOIs
StatePublished - Jun 1 1995

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