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The Journal of Neuroscience, July 1, 1999, 19(13):5185-5194

N-Type Calcium Channels and Their Regulation by GABA_B Receptors in Axons of Neonatal Rat Optic Nerve

Biao B. Sun¹ and Shing Yan Chiu^{1, 2}

¹ Graduate Program in Biophysics and ² Department of Physiology, University of Wisconsin School of Medicine, Madison, Wisconsin 53706

Axons of neonatal rat optic nerves exhibit fast calcium transients in response to brief action potential stimulation. In response to one to four closely spaced action potentials, evoked calcium transients showed a fast-rising phase followed by a decay with a time constant of ~2-3 sec. By selective staining of axons or glial cells with calcium dyes, it was shown that the evoked calcium transient originated from axons. The calcium transient was caused by influx because it was eliminated when bath calcium was removed. 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 little, if any, contribution. The identity of the residual calcium influx remains unclear. GABA application caused a dramatic reduction of the amplitude of the action potential and the associated calcium influx. When GABA_A receptors 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 was inhibited by the GABA_B receptor agonist baclofen. This baclofen effect was occluded by a previous block of N-type calcium channels and was unaffected by the broad-spectrum K⁺ channel blocker 4-AP. We conclude that neonatal rat optic nerve axons express N-type calcium channels, which are subjected to regulation by G-protein-coupled GABA_B receptors. We suggest that receptor-mediated inhibition of axonal calcium channels plays a protective role in neonatal anoxic and/or ischemic injury.

Key words: neonatal optic nerves; axons; calcium transient; GABA_B receptors; G-protein; axon-glia signaling; calcium channel regulation

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19135185-10$05.00/0

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