title: R-Type Ca2+channels couple to inhibitory neurotransmission to the longitudinal muscle in the guinea-pig ileum.
abstract: What is the central question of this study? Subtypes of enteric neurons are coded by the neurotransmitters they synthesize, but it is not known whether enteric neuron subtypes might also be coded by other proteins, including calcium channel subtypes controlling neurotransmitter release. What is the main finding and its importance? Our data indicate that guinea-pig ileum myenteric neuron subtypes may be coded by calcium channel subtypes. We found that R-type calcium channels are expressed by inhibitory but not excitatory longitudinal muscle motoneurons. R-Type calcium channels are also not expressed by circular muscle inhibitory motoneurons. Calcium channel subtype-selective antagonists could be used to target subtypes of neurons to treat gastrointestinal motility disorders. There is evidence that R-type Ca2+channels contribute to synaptic transmission in the myenteric plexus. It is unknown whether R-type Ca2+channels contribute to neuromuscular transmission. We measured the effects of the nitric oxide synthase inhibitor nitro-l-arginine (NLA), Ca2+channel blockers and apamin (SK channel blocker) on neurogenic relaxations and contractions of the guinea-pig ileum longitudinal muscle-myenteric plexus (LMMP) in vitro. We used intracellular recordings to measure inhibitory junction potentials. Immunohistochemical techniques localized R-type Ca2+channel protein in the LMMP and circular muscle. Cadmium chloride (pan-Ca2+channel blocker) blocked and NLA and NiCl2(R-type Ca2+channel blocker) reduced neurogenic relaxations in a non-additive manner. Nickel chloride did not alter neurogenic cholinergic contractions, but it potentiated neurogenic non-cholinergic contractions. Relaxations were inhibited by apamin, NiCl2and NLA and were blocked by combined application of these drugs. Relaxations were reduced by NiCl2or ω-conotoxin (N-type Ca2+channel blocker) and were blocked by combined application of these drugs. Longitudinal muscle inhibitory junction potentials were inhibited by NiCl2but not MRS 2179 (P2Y1receptor antagonist). Circular muscle inhibitory junction potentials were blocked by apamin, MRS 2179, ω-conotoxin and CdCl2but not NiCl2. We conclude that neuronal R-type Ca2+channels contribute to inhibitory neurotransmission to longitudinal muscle but less so or not all in the circular muscle of the guinea-pig ileum.
authors.affiliation: The Neuroscience Program, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Eileen S
authors.initials: ES
authors.lastname: Rodriguez-Tapia
authors.affiliation: The Neuroscience Program, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Vinogran
authors.initials: V
authors.lastname: Naidoo
authors.affiliation: Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: DeVries
authors.affiliation: Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Perez-Medina
authors.affiliation: The Neuroscience Program, Michigan State University, East Lansing, MI, 48824, USA.|Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: James J
authors.identifier: 0000-0001-7882-5596
authors.initials: JJ
authors.lastname: Galligan
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001120:Arginine / Q000378:metabolism; D019256:Cadmium Chloride / Q000494:pharmacology; D020908:Calcium Channels, R-Type / Q000378:metabolism*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D020908:Calcium Channels, R-Type; D018377:Neurotransmitter Agents; D019335:Nitroarginine; D001030:Apamin; D001120:Arginine; D019001:Nitric Oxide Synthase; D019256:Cadmium Chloride; D000109:Acetylcholine
keywords: calcium channel; nitric oxide; purinergic signaling; synaptic transmission