Ca²⁺ Channels and Synaptic Transmission at the Adult, Neonatal, and P/Q‐Type Deficient Neuromuscular Junction

Abstract

Different types of voltage-activated Ca(2+) channels have been established based on their molecular structure and pharmacological and biophysical properties. One of them, the P/Q-type, is the main channel involved in nerve-evoked neurotransmitter release at neuromuscular junctions and the immunological target in Eaton-Lambert Syndrome. At adult neuromuscular junctions, L- and N-type Ca(2+) channels become involved in transmitter release only under certain experimental or pathological conditions. In contrast, at neonatal rat neuromuscular junctions, nerve-evoked synaptic transmission depends jointly on both N- and P/Q-type channels. Synaptic transmission at neuromuscular junctions of the ataxic P/Q-type Ca(2+) channel knockout mice is also dependent on two different types of channels, N- and R-type. At both neonatal and P/Q knockout junctions, the K(+)-evoked increase in miniature endplate potential frequency was not affected by N-type channel blockers, but strongly reduced by both P/Q- and R-type channel blockers. These differences could be accounted for by a differential location of the channels at the release site, being either P/Q- or R-type Ca(2+) channels located closer to the release site than N-type Ca(2+) channels. Thus, Ca(2+) channels may be recruited to mediate neurotransmitter release where P/Q-type channels seem to be the most suited type of Ca(2+) channel to mediate exocytosis at neuromuscular junctions.

CaV2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis

“…P/Q-type, N-type and, to some extent, R-type channels are highly expressed at presynaptic nerve terminals where their activities evoke neurotransmitter release (Katz et al 1996, Iwasaki et al 2000, Nudler et al 2003, Trimmer and Rhodes 2004.…”

Conus Venom Peptide Pharmacology

“…Peripheral side effects expected from autonomic and neuromuscular block. Bourinet et al, 1999;Nudler et al, 2003;Catterall et al, 2005bCatterall et al, , 2007 (For selectivity see Table 4.) Spider toxins: -agatoxin IVA Ca v 2.2 (CACNA1B) splice variants Brain, spinal cord, sympathetic neurons, DRG, contribution to presynaptic neurotransmitter release in CNS and PNS.…”

The role of synaptic laminins-α4 and -β2 in maturation and maintenance of the neuromuscular synapse

“…The switch from N-to P/Q-type VGCCs, as the predominant calcium channel for neurotransmitter release in mature NMJ is associated with its closer localisation to release sites (Urbano et al, 2002;Nudler et al, 2003). This is in agreement with the study by Rosato-Siri et al (2002) which demonstrated ineffective binding of BAPTA, a fast calcium ion chelator to calcium ions that enter through P/Q-type VGCCs.…”

“…Thus, P/Q-type VGCCs and the direct interaction with laminin-β2 are necessary for efficient organisation of active zone elements. This could be due to the closer localisation of P/Q-type to release sites, being more favourable in interaction with presynaptic components in comparison with N-type VGCCs which are localised further away from the release sites (Urbano et al, 2002;Nudler et al, 2003) despite both VGCCs having direct interaction with presynaptic proteins such as Bassoon, SNAP25 and Syntaxin 1A (Kim & Catterall, 1997;Zhong et al, 1999;Chen et al, 2011;Nishimune et al, 2012).…”

“…In contrast, most of the calcium ions which entered through N-type VGCCs were bound by BAPTA (RosatoSiri et al, 2002). This suggests the locale of N-type VGCCs is distal from the release sites, therefore calcium ions entering through this channel need to travel a greater distance to reach the release sites resulting in increased binding of calcium ions by BAPTA (Wu et al, 1999;Nudler et al, 2003). Thus, P/Q-type VGCCs are suggested to be the dominant mediator in neurotransmitter release at mature and adult NMJs.…”