title: Acetylcholine release at neuromuscular junctions of adult tottering mice is controlled by N-(cav2.2) and R-type (cav2.3) but not L-type (cav1.2) Ca2+ channels.
abstract: The mutation in the alpha(1A) subunit gene of the P/Q-type (Ca(v)2.1) Ca(2+) channel present in tottering (tg) mice causes ataxia and motor seizures that resemble absence epilepsy in humans. P/Q-type Ca(2+)channels are primarily involved in acetylcholine (ACh) release at mammalian neuromuscular junctions. Unmasking of L-type (Ca(v)1.1-1.2) Ca(2+) channels occurs in cerebellar Purkinje cells of tg mice. However, whether L-type Ca(2+) channels are also up-regulated at neuromuscular junctions of tg mice is unknown. We characterized thoroughly the pharmacological sensitivity of the Ca(2+) channels, which control ACh release at adult tg neuromuscular junctions. Block of N- and R-type (Ca(v)2.2-2.3), but not L-type Ca(2+) channels, significantly reduced quantal content of end-plate potentials in tg preparations. Neither resting nor KCl-evoked miniature end-plate potential frequency differed significantly between tg and wild type (WT). Immunolabeling of Ca(2+) channel subunits alpha(1A), alpha(1B), alpha(1C), and alpha(1E) revealed an apparent increase of alpha(1B), and alpha(1E) staining, at tg but not WT neuromuscular junctions. This presumably compensates for the deficit of P/Q-type Ca(2+)channels, which localized presynaptically at WT neuromuscular junctions. No alpha(1C) subunits juxtaposed with pre- or postsynaptic markers at either WT or tg neuromuscular junctions. Thus, in adult tg mice, immunocytochemical and electrophysiological data indicate that N- and R-type channels both assume control of ACh release at motor nerve terminals. Recruitment of alternate subtypes of Ca(2+) channels to control transmitter release seems to represent a commonly occurring method of neuronal plasticity. However, it is unclear which conditions underlie recruitment of Ca(v)2 as opposed to Ca(v)1-type Ca(2+) channels.
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, B-331 Life Sciences Bldg., East Lansing, MI 48824-1317, USA.
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Pardo
authors.forename: Ravindra K
authors.initials: RK
authors.lastname: Hajela
authors.forename: William D
authors.initials: WD
authors.lastname: Atchison
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000502:physiology*; D020908:Calcium Channels, R-Type / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D007150:Immunohistochemistry; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D018613:Microscopy, Confocal; D009045:Motor Endplate / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D020908:Calcium Channels, R-Type; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D011189:Potassium Chloride; D000109:Acetylcholine