R-type Ca(2+) channels contribute to fast synaptic  excitation and action potentials in subsets of myenteric  neurons in the guinea pig intestine.
BACKGROUND
R-type Ca(2+) channels are expressed by myenteric neurons in the guinea pig ileum but the specific function of these channels is unknown.


METHODS
In the present study, we used intracellular electrophysiological techniques to determine the function of R-type Ca(2+) channels in myenteric neurons in the acutely isolated longitudinal musclemyenteric plexus. We used immunohistochemical methods to localize the Ca(V)2.3 subunit of the R-type Ca(2+) channel in myenteric neurons. We also studied the effects of the non-selective Ca(2+) channel antagonist, CdCl₂ (100 μmol L⁻¹), the R-type Ca(2+) channel blockers NiCl₂ (50 μmol L⁻¹) and SNX-482 (0.1 μmol L⁻¹), and the N-type Ca(2+) channel blocker x-conotoxin GVIA (CTX 0.1 μmol L⁻¹) on action potentials and fast and slow excitatory postsynaptic potentials (fEPSPs and sEPSPs) in S and AH neurons in vitro.


RESULTS
Ca(V)2.3 co-localized with calretinin and calbindin in myenteric neurons. NiCl₂ and SNX-482 reduced the duration and amplitude of action potentials in AH but not S neurons. NiCl₂ inhibited the afterhyperpolarization in AH neurons. x-conotoxin GVIA, but not NiCl₂, blocked sEPSPs in AH neurons. NiCl₂ and SNX-482 inhibited cholinergic, but not cholinergic/purinergic, fEPSPs in S neurons.


CONCLUSIONS
These data show that R-type Ca(2+) channels contribute to action potentials, but not slow synaptic transmission, in AH neurons. R-type Ca(2+) channels contribute to release of acetylcholine as the mediator of fEPSPs in some S neurons. These data indicate that R-type Ca(2+) channels may be a target for drugs that selectively modulate activity of AH neurons or could alter fast synaptic excitation in specific pathways in the myenteric plexus.
Naidoo
V
V
Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA.
Dai
X
X
Galligan
J J
JJ
D000109:Acetylcholine / Q000378:metabolism; D000200:Action Potentials / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D019256:Cadmium Chloride / Q000494:pharmacology; D064032:Calbindin 2; D064026:Calbindins; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020908:Calcium Channels, R-Type / Q000378:metabolism*; D002478:Cells, Cultured; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005730:Ganglionic Blockers / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009197:Myenteric Plexus / Q000166:cytology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009532:Nickel / Q000494:pharmacology; D021122:Protein Subunits / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013111:Spider Venoms / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D064032:Calbindin 2; D064026:Calbindins; D002121:Calcium Channel Blockers; D020908:Calcium Channels, R-Type; D005730:Ganglionic Blockers; D021122:Protein Subunits; D064030:S100 Calcium Binding Protein G; C115521:SNX 482; D013111:Spider Venoms; C022838:nickel chloride; D008464:Mecamylamine; D009532:Nickel; D000255:Adenosine Triphosphate; D020866:omega-Conotoxin GVIA; D019256:Cadmium Chloride; D000109:Acetylcholine