TY - JOUR T1 - 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 JF - The Journal of Neuroscience JO - J. Neurosci. SP - 1839 LP - 1851 DO - 10.1523/JNEUROSCI.13-05-01839.1993 VL - 13 IS - 5 AU - O Braha AU - B Edmonds AU - T Sacktor AU - ER Kandel AU - M Klein Y1 - 1993/05/01 UR - http://www.jneurosci.org/content/13/5/1839.abstract N2 - 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. ER -