The Journal of Neuroscience, July 1, 1999, 19(13):5185-5194
N-Type Calcium Channels and Their Regulation by GABAB
Receptors in Axons of Neonatal Rat Optic Nerve
Biao B.
Sun1 and
Shing
Yan
Chiu1, 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
GABAA 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 GABAB
receptors. Indeed, the calcium influx was inhibited by the
GABAB 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 GABAB 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; GABAB receptors; G-protein; axon-glia signaling; calcium
channel regulation
Copyright © 1999 Society for Neuroscience 0270-6474/99/19135185-10$05.00/0