Ca 2+ Channels and Synaptic Transmission at the Adult, Neonatal, and P/Q‐Type Deficient Neuromuscular Junction

A bstract : 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.