Journal of Neuroscience, Vol 9, 480-487, Copyright © 1989 by Society for Neuroscience
Inhibitors of protein kinase C prevent enhancement of calcium current and action potentials in peptidergic neurons of Aplysia
PJ Conn, JA Strong and LK Kaczmarek
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
Following brief stimulation of an afferent pathway, the bag cell neurons of
Aplysia undergo a dramatic change in excitability, resulting in a prolonged
discharge of spontaneous action potentials. During the discharge, the
action potentials of the bag cell neurons become enhanced in height and
width. The afterdischarge triggers release of neuroactive peptides that
initiate egg-laying behavior in this animal. Evidence suggests that changes
in excitability of the bag cell neurons may be mediated by activation of
protein kinase C (PKC) and cAMP- dependent protein kinase (cAMP-PK). PKC
activators, such as the phorbol ester TPA (12-O-tetradecanoyl-13-phorbol
acetate), enhance the amplitude of action potentials in isolated bag cell
neurons in cell culture. These agents act by unmasking a previously covert
species of voltage-dependent calcium channel resulting in an increase in
calcium current. In the accompanying paper (Conn et al., 1989), we showed
that H-7, a protein kinase inhibitor, inhibits the effect of TPA, and is a
selective inhibitor of PKC relative to cAMP-PK in these cells. We now
report that another PKC inhibitor, sphinganine, also inhibits the effect of
TPA on action potential height and calcium current in cultured bag cell
neurons, and that N-acetylsphinganine, an inactive sphinganine analog,
fails to inhibit the effects of PKC activators. Although both H-7 and
sphinganine prevent the effects of TPA when added prior to TPA addition,
neither compound reverses the effects of TPA when added after the action
potentials have already become enhanced by TPA.(ABSTRACT TRUNCATED AT 250
WORDS)
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