The Journal of Neurophysiology Vol. 78 No. 6 December 1997, pp. 3359-3370
Copyright ©1997 The American Physiological Society

Regulation of N- and L-Type Ca²⁺ Channels in Adult Frog Sympathetic Ganglion B Cells by Nerve Growth Factor In Vitro and In Vivo

Saobo Lei, William F. Dryden, and Peter A. Smith

Department of Pharmacology and Division of Neuroscience, University of Alberta, Edmonton, Alberta T6G 2H7, Canada

Lei, Saobo, William F. Dryden, and Peter A. Smith. Regulation of N- and L-type Ca²⁺ channels in adult frog sympathetic ganglion B cells by nerve growth factor in vitro and in vivo. J. Neurophysiol. 78: 3359-3370, 1997. To examine mechanisms responsible for the long-term regulation of Ca²⁺-channels in an adult neuron, changes in whole cell Ba²⁺ current (I_Ba) were examined in adult bullfrog sympathetic ganglion B cells in vitro. Cells were cultured at low density in defined, serum free medium. After 15 days, total I_Ba was similar to the initial value, whereas I_Ba density was reduced by ~36%, presumably due to an increase in neuronal surface area. By contrast, I_Ba density remained constant after 6-15 days in the presence of murine -NGF (200 ng/ml), and total I_Ba was almost doubled. Inclusion of cytosine arabinoside (Ara-C; 10 µM) to inhibit proliferation of nonneuronal cells, did not affect the survival of neurons in the absence of nerve growth factor (NGF) nor did it attenuate I_Ba. Ara-C did not prevent the effect of NGF on I_Ba. There were three independent components to the action of NGF; during 6-9 days, it increased -conotoxin-GVIA-sensitive N-type I_Ba (I_Ba,N); increased nifedipine-sensitive L-type I_Ba (I_Ba,L) and decreased inactivation of the total Ba²⁺ conductance (g_Ba). The latter effect involved a selective decrease in the amplitude of one of the four kinetic components that describe the inactivation process. Total I_Ba was also 55.8% larger than control in the somata of B cells acutely dissociated from leopard frogs that had received prior subcutaneous injections of NGF. By contrast, injection of NGF antiserum decreased total I_Ba by 29.4%. There was less inactivation of g_Ba in B cells from NGF-injected animals than in cells from animals injected with NGF antiserum (P < 0.001). These data suggest that NGF-like molecule(s) play(s) a role in the maintenance of I_Ba in an adult amphibian sympathetic neuron; the presence of NGF may allow the neuron to maintain a constant relationship between cell size and current density. They also show that I_Ba inactivation in an adult neuron can be modulated in a physiologically relevant way by an extracellular ligand.

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