TY - JOUR T1 - Acetylcholine Release at Neuromuscular Junctions of Adult Tottering Mice Is Controlled by N-(Ca<sub>v</sub>2.2) and R-Type (Ca<sub>v</sub>2.3) but Not L-Type (Ca<sub>v</sub>1.2) Ca<sup>2+</sup> Channels JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1009 LP - 1020 DO - 10.1124/jpet.106.108670 VL - 319 IS - 3 AU - Nicole E. Pardo AU - Ravindra K. Hajela AU - William D. Atchison Y1 - 2006/12/01 UR - http://jpet.aspetjournals.org/content/319/3/1009.abstract N2 - The mutation in the α1A subunit gene of the P/Q-type (Cav2.1) Ca2+ channel present in tottering (tg) mice causes ataxia and motor seizures that resemble absence epilepsy in humans. P/Q-type Ca2+channels are primarily involved in acetylcholine (ACh) release at mammalian neuromuscular junctions. Unmasking of L-type (Cav1.1–1.2) Ca2+ channels occurs in cerebellar Purkinje cells of tg mice. However, whether L-type Ca2+ channels are also up-regulated at neuromuscular junctions of tg mice is unknown. We characterized thoroughly the pharmacological sensitivity of the Ca2+ channels, which control ACh release at adult tg neuromuscular junctions. Block of N- and R-type (Cav2.2–2.3), but not L-type Ca2+ 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 Ca2+ channel subunits α1A, α1B, α1C, and α1E revealed an apparent increase of α1B, and α1E staining, at tg but not WT neuromuscular junctions. This presumably compensates for the deficit of P/Q-type Ca2+channels, which localized presynaptically at WT neuromuscular junctions. No α1C 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 Ca2+ channels to control transmitter release seems to represent a commonly occurring method of neuronal plasticity. However, it is unclear which conditions underlie recruitment of Cav2 as opposed to Cav1-type Ca2+ channels. ER -