Adenosine inhibits N-type calcium channels at the rat neuromuscular junction.

1. In earlier studies, it has been reported that under in vitro conditions transmitter release at the rat neuromuscular junction is normally suppressed due to the effect of adenosine release from the isolated tissue. In the present study we wanted to determine whether this action may involve the inhibition of calcium influx through adenosine-sensitive calcium channels. 2. In order to test this hypothesis, we examined the role of N-type calcium channels in regulating nerve-evoked transmitter release by using the N-type calcium channel-specific blocker omega-conotoxin GVIA (CTX). In order to control the inhibitory action of adenosine, we also used the adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). We tested the effect of blocking N-type calcium channels with CTX in the presence and absence of DPCPX. We examined the effects of these drugs on quantal transmitter release in the transected preparation of the phrenic nerve-hemidiaphragm of the rat using intracellular recording techniques. 3. At 10 nmol/L, CTX alone had no effect on nerve-evoked transmitter release; however, in the presence of 0.1 micro mol/L DPCPX, CTX significantly depressed nerve-evoked transmitter release. 4. These data support the view that adenosine inhibits nerve-evoked transmitter release by inhibiting N-type calcium channels on nerve terminals.