O. Braha et al., THE CONTRIBUTIONS OF PROTEIN KINASE-A AND PROTEIN-KINASE-C TO THE ACTIONS OF 5-HT ON THE L-TYPE CA-2+ CURRENT OF THE SENSORY NEURONS IN APLYSIA, The Journal of neuroscience, 13(5), 1993, pp. 1839-1851
In the sensory neurons of Aplysia, 5-HT acts through cAMP to reduce cu
rrent flow through two classes of K+ channels, the S-K+channel and a t
ransient K+ channel(I(KV)). In addition, 5-HT increases a voltage-depe
ndent, nifedipine-sensitive Ca 2 +current. In this article we show tha
t, while the effect on the S-K+ channel is mediated exclusively by cAM
P, the effect on the Ca2+ current can be mimicked by phorbol 12,13-dib
utyrate (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 mediati
ng the effect of 5-HT on the nifedipine-sensitive Ca2+ current. We fin
d that H-7, a kinase inhibitor that appears to inhibit PKC more effect
ively than PKA in intact Aplysia neurons, reverses the increase in the
Ca2+ current produced by PDBu. Moreover, H-7 partially blocks the eff
ect 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 produc
ed 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+ cu
rrent produced by 5-HT, suggesting that the effect of 5-HT on this cur
rent 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 bas
is of the time course of their appearance. The fact that the decrease
in the S-K+ current precedes the increase in Ca2+ current suggests tha
t there may be a temporal difference in the activation of the two kina
se systems.