Inactivating and noninactivating Ca(2+)- and voltage-dependent K+ current in rat adrenal chromaffin cells.
The properties of Ca(2+)- and voltage-dependent K+ currents and their role in defining membrane potential were studied in cultured rat chromaffin cells. Two variants of large-conductance, Ca2+ and voltage-dependent BK channels, one noninactivating and one inactivating, were largely segregated among patches. Whole-cell noninactivating and inactivating currents resulting from each of these channels were segregated among different chromaffin cells. Cell-to-cell variation in the rate and extent of whole-cell current decay was not explained by differences in cytosolic [Ca2+] regulation among cells; rather, variation was due to differences in the intrinsic properties of the underlying BK channels. About 75% of rat chromaffin cells and patches express inactivating BK current (termed BKi) while the remainder express noninactivating BK current (termed BKs). The activation time course of both currents is similar, as is the dependence of activation on [Ca2+] and membrane potential. However, deactivation of BKi channels is slower than that of BKs channels. The functional role of these BK channel variants was studied in current-clamp recordings. Although both BKi and BKs currents contribute to action potential repolarization, cells expressing BKi current are better able to fire repetitively in response to constant current injection. Blockade of BKi current by charybdotoxin abolishes this behavior, showing that afterhyperpolarizations mediated by BKi current are permissive for repetitive firing. Thus, important properties of chromaffin cell membrane excitability are determined by the type of BK current expressed.
Solaro
C R
CR
Washington University School of Medicine, Department of Anesthesiology, St. Louis, Missouri 63110, USA.
Prakriya
M
M
Ding
J P
JP
Lingle
C J
CJ
D000311:Adrenal Glands / Q000166:cytology / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D018999:Charybdotoxin; D002838:Chromaffin System / Q000166:cytology / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D004594:Electrophysiology; D009994:Osmolar Concentration; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000502:physiology; D012604:Scorpion Venoms / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013997:Time Factors; D014118:Toxins, Biological / Q000494:pharmacology
D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011976:Receptors, Muscarinic; D012604:Scorpion Venoms; D013757:Tetraethylammonium Compounds; D014118:Toxins, Biological; D018999:Charybdotoxin; D019789:Tetraethylammonium; C064719:iberiotoxin; D002118:Calcium