J Physiol Volume 566, Number 3, 681-688, August 1, 2005 DOI: 10.1113/jphysiol.2005.090647
Modulation of calcium currents is eliminated after cleavage of a strategic component of the mammalian secretory apparatus
Eugene M Silinsky1
1 Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA
Adenosine inhibits neurotransmitter secretion from motor nerves by an effect on the secretory apparatus in amphibia. In contrast, the inhibitory effect of adenosine is associated with decreases in calcium currents at mouse motor nerve endings. To determine if the action of adenosine in the mouse is mediated thorough a direct effect on calcium channels or through the secretory machinery, the effects of cleavage of the SNARE proteins on the action of adenosine were examined. Cleavage of the SNARE syntaxin with botulinum toxin type C (Botx/C) prevented the inhibitory effect of adenosine on nerve terminal calcium currents. Cleavage of the other SNAREs (synaptobrevin with Botx/D or SNAP-25 with Botx/A) failed to affect the inhibitory action of adenosine. The results provide evidence for an intimate coupling of nerve terminal calcium channels with a plasma membrane component of the SNARE complex, such that modulation of calcium currents by a G-protein coupled receptor cannot occur when syntaxin is cleaved.
(Received 16 May 2005;
accepted after revision 15 June 2005;
first published online 16 June 2005)
Corresponding author E. M. Silinsky: Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA. Email: e-silinsky{at}northwestern.edu
Copyright © 2005 The Physiological Society.