N-type calcium channels and their regulation by GABA(B) receptors in axonsof neonatal rat optic nerve

Axons of neonatal rat optic nerves exhibit fast calcium transients in respo nse to brief action potential stimulation. In response to one to four close ly spaced action potentials, evoked calcium transients showed a fast-rising phase followed by a decay with a time constant of similar to 2-3 sec. By s elective staining of axons or glial cells with calcium dyes, it was shown t hat the evoked calcium transient originated from axons. The calcium transie nt was caused by influx because it was eliminated when bath calcium was rem oved. Pharmacological profile studies with calcium channel subtype-specific peptides suggested that 58% of the evoked calcium influx was accounted for by N-type calcium channels, whereas L- and P/Q-type calcium channels had l ittle, if any, contribution. The identity of the residual calcium influx re mains unclear. GABA application caused a dramatic reduction of the amplitud e of the action potential and the associated calcium influx. When GABA(A) r eceptors were blocked by bicuculline, the inhibitory effect of GABA on the action potential was eliminated, whereas that on the calcium influx was not , indicating involvement of GABA(B) receptors. Indeed, the calcium influx w as inhibited by the GABA(B) receptor agonist baclofen. This baclofen effect was occluded by a previous block of N-type calcium channels and was unaffe cted by the broad-spectrum K+ channel blocker 4-AP. We conclude that neonat al rat optic nerve axons express N-type calcium channels, which are subject ed to regulation by G-protein-coupled GABA(B) receptors. We suggest that re ceptor-mediated inhibition of axonal calcium channels plays a protective ro le in neonatal anoxic and/or ischemic injury.