Muscarinic activation and calcium permeation of non-selective
cation currents in airway myocytes.
Fleischmann, Bernd K., Yong-Xiao Wang, Michael I. Kotlikoff.
Department of Animal Biology, School of Veterinary Medicine,
University of Pennsylvania, Philadelphia, PA 19104-6046
APStracts 3:0272C, 1996.
We examined the activation and calcium permeation of non-selective
cation channels in voltage-clamped (nystatin), fura 2 -loaded equine
tracheal myocytes at 35 degrees C. Methacholine (mACh, 50 [mu]M)
induced a biphasic increase in [Ca++]i and a biphasic inward current
consisting of a large, rapidly inactivating calcium-activated
chloride current (I(Cl)Ca) and a smaller, sustained non-selective
cation current (Icat). I(Cl)Ca but not ICat was activated by
caffeine. Neither ICat nor the sustained rise in [Ca++]i were blocked
by nisoldipine, whereas both were rapidly blocked by Ni++. ICat was
determined to be calcium permeant since: 1) a sustained elevation of
[Ca++]i occurred when ICat was activated, and blockade of ICat
produced a rapid decline in [Ca++]i; 2) increasing extracellular Ca++
during ICat increased [Ca++]i; 3) 110 mM extracellular Ca++ shifted
the reversal potential of ICat to 12 mV (Ca++/Cs+ permeability ratio
= 3.6); 4 instantaneous voltage-clamp steps to negative potentials
during ICat increased the current and [Ca++]i, whereas depolarizing
steps decreased the current and [Ca++]i. The fraction of ICat carried
by calcium under physiological conditions was estimated to be 14% at
-60 mV.
Received 6 June 1996; accepted in final form 7 August 1996.
APS Manuscript Number C319-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996