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

J Physiol. 1995 Jun 1;485 ( Pt 2)(Pt 2):297-318. doi: 10.1113/jphysiol.1995.sp020731.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Caffeine / pharmacology
  • Calcium / metabolism
  • Calcium / physiology*
  • Chromaffin System / cytology
  • Chromaffin System / metabolism*
  • Electrophysiology
  • In Vitro Techniques
  • Ionomycin / pharmacology
  • Membrane Potentials / drug effects
  • Muscarine / pharmacology
  • Muscarinic Agonists*
  • Patch-Clamp Techniques
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism*
  • Rats
  • Receptors, Muscarinic / metabolism

Substances

  • Muscarinic Agonists
  • Potassium Channels
  • Receptors, Muscarinic
  • Caffeine
  • Ionomycin
  • Muscarine
  • Calcium