Helli PB, Pertens E, Janssen LJ.Cyclopiazonic acid activates
a Ca2+-permeable, nonselective cation conductance in porcine and
bovine tracheal smooth muscle.
J Appl Physiol. 2005 Nov;99(5):1759-68. Epub 2005 Jul 14.
Firestone Institute for Respiratory Health, St. Joseph's
Healthcare, Department of Medicine, McMaster University,
Hamilton, Ontario, Canada.
Capacitative Ca2+ entry has been examined in several tissues
and, in some, appears to be mediated by nonselective cation
channels collectively referred to as "store-operated" cation
channels; however, relatively little is known about the
electrophysiological properties of these channels in airway
smooth muscle. Consequently we examined the electrophysiological
characteristics and changes in intracellular Ca2+ concentration
associated with a cyclopiazonic acid (cyclopiazonic acid
(CPA))-evoked current in porcine and bovine airway smooth muscle
using patch-clamp and Ca2+-fluorescence techniques. In bovine
tracheal myocytes, cyclopiazonic acid (CPA) induced an elevation
of intracellular Ca2+ that was dependent on extracellular Ca2+
and was insensitive to nifedipine (an L-type voltage-gated Ca2+
channel inhibitor). Using patch-clamp techniques and conditions
that block both K+ and Cl- currents, we found that cyclopiazonic
acid (CPA) rapidly activated a membrane conductance
(I(cyclopiazonic acid (CPA))) in porcine and bovine tracheal
myocytes that exhibits a linear current-voltage relationship
with a reversal potential around 0 mV. Replacement of
extracellular Na+ resulted in a marked reduction of
I(cyclopiazonic acid (CPA)) at physiological membrane potentials
(i.e., -60 mV) that was accompanied by a shift in the reversal
potential for I(cyclopiazonic acid (CPA)) toward more negative
membrane potentials. In addition, I(cyclopiazonic acid (CPA))
was markedly inhibited by 10 microM Gd3+ and La3+ but was
largely insensitive to 1 microM nifedipine. We conclude that
cyclopiazonic acid (CPA) induces capacitative Ca2+ entry in
porcine and bovine tracheal smooth muscle via a Gd3+- and
La3+-sensitive, nonselective cation conductance.
PMID: 16024526
|
