| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Journal of Neurophysiology Vol. 88 No. 1 July 2002, pp. 277-288
Copyright ©2002 by the American Physiological Society
Department of Pharmacology and University Centre for Neuroscience, University of Alberta, Edmonton, Alberta T6G 2H7, Canada
Stemkowski, Patrick L.,
Frederick W. Tse,
Vera Peuckmann,
Christopher P. Ford,
William F. Colmers, and
Peter A. Smith.
ATP-Inhibition of M Current in Frog Sympathetic Neurons Involves
Phospholipase C But Not Ins P3, Ca2+, PKC, or
Ras. J. Neurophysiol. 88: 277-288, 2002. Suppression of the voltage-activated,
noninactivating K+ conductance (M conductance;
gM) by muscarinic agonists,
P2Y agonists or bradykinin increases neuronal
excitability. All agonist effects are mediated, at least in part, via
the Gq/11 class of G protein. We found, using
whole cell or perforated patch recording from bullfrog sympathetic B
neurons that ATP-induced suppression of gM was
attenuated by the phospholipase C (PLC) inhibitor, U73122 (IC50 ~0.14 µM) but not by the inactive
isomer, U73343. The ability of extracellularly applied U73122 to
inhibit PLC was confirmed by its antagonism of ATP-induced elevation of
intracellular Ca2+ as measured by fura-2
photometry. ATP-induced gM suppression was not antagonized by the protein kinase C (PKC) inhibitor,
chelerythrine (5 µM extracellular +10 µM intracellular), by the
Ca2+-ATPase inhibitor, thapsigargin (5 µM), or
by inositol trisphosphate (InsP3) receptor
antagonists, heparin (~300 µM) or xestospongin C (1.8 µM). The
effect of ATP on gM was thus dependent
on PLC yet independent of PKC and of
InsP3-induced release of intracellular Ca2+. We therefore tested the involvement of a
PKC-independent action of diacylglycerol (DAG) that could occur via
activation of Ras. This low-molecular-weight G protein is
activated following DAG binding to Ras-GRP, a neuronal
Ras-GTP exchange factor. However, impairment of
Ras function by culturing neurons with isoprenylation inhibitors (perillic acid, 0.1 mM, or 
-hydroxyfarnesyl-phosphonic acid, 10 µM) failed to affect ATP-induced
gM suppression. Inhibition of MEK
(mitogen-activated protein kinase), a downstream target of
Ras, by using PD 98059 (10 µM) was also ineffective. The
transduction mechanism used by ATP to suppress gM
in frog sympathetic neurons therefore differs from the PLC-independent
mechanism used by muscarine and from the PLC and
Ca2+-dependent mechanism used by bradykinin and
UTP in mammalian ganglia. The possibility remains that
"lipid-signaling" mechanisms, perhaps involving PLC-induced
depletion of phosphatidylinositol bisphosphate, are involved in
PLC-mediated inhibition of gM by ATP
in amphibian sympathetic neurons.
This article has been cited by other articles:
|
|
 |
|
  C. P. Ford, K. V. Wong, V. B. Lu, E. Posse de Chaves, and P. A. Smith Differential Neurotrophic Regulation of Sodium and Calcium Channels in an Adult Sympathetic Neuron J Neurophysiol, March 1, 2008; 99(3): 1319 - 1332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Zaika, G. P. Tolstykh, D. B. Jaffe, and M. S. Shapiro Inositol Triphosphate-Mediated Ca2+ Signals Direct Purinergic P2Y Receptor Regulation of Neuronal Ion Channels J. Neurosci., August 15, 2007; 27(33): 8914 - 8926. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Burnstock Physiology and Pathophysiology of Purinergic Neurotransmission Physiol Rev, April 1, 2007; 87(2): 659 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Filippov, R. C. Y. Choi, J. Simon, E. A. Barnard, and D. A. Brown Activation of P2Y1 Nucleotide Receptors Induces Inhibition of the M-Type K+ Current in Rat Hippocampal Pyramidal Neurons J. Neurosci., September 6, 2006; 26(36): 9340 - 9348. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. F. Horowitz, W. Hirdes, B.-C. Suh, D. W. Hilgemann, K. Mackie, and B. Hille Phospholipase C in Living Cells: Activation, Inhibition, Ca2+ Requirement, and Regulation of M Current J. Gen. Physiol., August 29, 2005; 126(3): 243 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Wei, A. Butler, and L. Salkoff KCNQ-like Potassium Channels in Caenorhabditis elegans: CONSERVED PROPERTIES AND MODULATION J. Biol. Chem., June 3, 2005; 280(22): 21337 - 21345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Ford, P. L. Stemkowski, P. E. Light, and P. A. Smith Experiments to Test the Role of Phosphatidylinositol 4,5-Bisphosphate in Neurotransmitter-Induced M-Channel Closure in Bullfrog Sympathetic Neurons J. Neurosci., June 15, 2003; 23(12): 4931 - 4941. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ishibashi, M. Umezu, I.-S. Jang, Y. Ito, and N. Akaike {alpha}1-Adrenoceptor-activated cation currents in neurones acutely isolated from rat cardiac parasympathetic ganglia J. Physiol., April 1, 2003; 548(1): 111 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Guo and G. G Schofield Activation of a PTX-insensitive G protein is involved in histamine-induced recombinant M-channel modulation J. Physiol., December 15, 2002; 545(3): 767 - 781. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
