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Journal of Neuroscience, Vol 13, 1839-1851, Copyright © 1993 by Society for Neuroscience
The contributions of protein kinase A and protein kinase C to the actions of 5-HT on the L-type Ca2+ current of the sensory neurons in Aplysia
O Braha, B Edmonds, T Sacktor, ER Kandel and M Klein
Worcester Foundation for Experimental Biology, Shrewsbury, Massachusetts 01545.
In the sensory neurons of Aplysia, 5-HT acts through cAMP to reduce current
flow through two classes of K+ channels, the S-K + channel and a transient
K+ channel (Ikv). In addition, 5-HT increases a voltage- dependent,
nifedipine-sensitive Ca2+ current. In this article we show that, while the
effect on the S-K+ channel is mediated exclusively by cAMP, the effect on
the Ca2+ current can be mimicked by phorbol 12,13- dibutyrate (PDBu) as
well as by intracellular injection of cAMP. We then use specific blockers
of protein kinase C (PKC) and the cAMP- dependent protein kinase A (PKA) to
examine the roles of PKC and PKA in mediating the effect of 5-HT on the
nifedipine-sensitive Ca2+ current. We find that H-7, a kinase inhibitor
that appears to inhibit PKC more effectively than PKA in intact Aplysia
neurons, reverses the increase in the Ca2+ current produced by PDBu.
Moreover, H-7 partially blocks the effect of 5-HT on the Ca2+ current
without affecting the decrease in the S-K+ current. A more specific PKC
inhibitor (the 19-31 pseudosubstrate of PKC) also partially blocks the
increase in the Ca2+ current produced by 5-HT, suggesting that this
increase is mediated by PKC. Rp-cAMPS, a specific blocker of PKA, did not
block the increase in the Ca2+ current produced by 5-HT, suggesting that
the effect of 5-HT on this current may be mediated to only a small extent
by PKA. The effect of 5-HT on the S-K+ current and the Ca2+ current can
also be separated on basis of the time course of their appearance. The fact
that the decrease in the S-K+ current precedes the increase in Ca2+ current
suggests that there may be a temporal difference in the activation of the
two kinase systems.
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