title: Redundancy of Cav2.1 channel accessory subunits in transmitter release at the mouse neuromuscular junction.
abstract: Ca(v)2.1 (P/Q-type) channels possess a voltage-sensitive pore-forming alpha(1) subunit that can associate with the accessory subunits alpha(2)delta, beta and gamma. The primary role of Ca(v)2.1 channels is to mediate transmitter release from nerve terminals both in the central and peripheral nervous system. Whole-cell voltage-clamp studies in in vitro expression systems have indicated that accessory channel subunits can have diverse modulatory effects on membrane expression and biophysical properties of Ca(v)2.1 channels. However, there is only limited knowledge on whether similar modulation also occurs in the specific presynaptic environment in vivo and, hence, whether accessory subunits influence neurotransmitter release. Ducky, lethargic and stargazer are mutant mice that lack functional alpha(2)delta-2, beta(4) and gamma(2) accessory Ca(v) channel subunits, respectively. The neuromuscular junction (NMJ) is a peripheral synapse, where transmitter release is governed exclusively by Ca(v)2.1 channels, and which can be characterized electrophysiologically with relative experimental ease. In order to investigate a possible synaptic influence of accessory subunits in detail, we electrophysiologically measured acetylcholine (ACh) release at NMJs of these three mutants. Surprisingly, we did not find any changes compared to wild-type littermates, other than a small reduction (25%) of evoked ACh release at ducky NMJs. This effect is most likely due to the approximately 40% reduced synapse size, associated with the reduced size of ducky mice, rather than resulting directly from reduced Ca(v)2.1 channel function due to alpha(2)delta-2 absence. We conclude that alpha(2)delta-2, beta(4), and gamma(2) accessory subunits are redundant for the transmitter release-mediating function of presynaptic Ca(v)2.1 channels at the mouse NMJ.
authors.affiliation: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Simon
authors.initials: S
authors.lastname: Kaja
authors.forename: Boyan
authors.initials: B
authors.lastname: Todorov
authors.forename: Rob C G
authors.initials: RC
authors.lastname: van de Ven
authors.forename: Michel D
authors.initials: MD
authors.lastname: Ferrari
authors.forename: Rune R
authors.initials: RR
authors.lastname: Frants
authors.forename: Arn M J M
authors.initials: AM
authors.lastname: van den Maagdenberg
authors.forename: Jaap J
authors.initials: JJ
authors.lastname: Plomp
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002038:Bungarotoxins / Q000493:pharmacokinetics; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000172:deficiency; D020864:Calcium Channels, N-Type / Q000235:genetics / Q000378:metabolism*; D003964:Diaphragm / Q000166:cytology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D053609:Lethargy / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D008817:Mice, Mutant Strains; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D021122:Protein Subunits / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D000109:Acetylcholine; D002038:Bungarotoxins; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D021122:Protein Subunits; C491528:Cacnb2 protein, mouse