Modulation of calcium currents is eliminated after cleavage of a strategic component of the mammalian secretory apparatus.
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.
Silinsky
Eugene M
EM
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA. e-silinsky@northwestern.edu
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology*; D050600:SNARE Proteins; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D033921:Vesicular Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
D015220:Calcium Channels; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; D001905:Botulinum Toxins; C096324:botulinum toxin type C; D000241:Adenosine; D002118:Calcium