MODULATION OF A TRANSIENT K+ CURRENT IN THE PLEURAL SENSORY NEURONS OF APLYSIA BY SEROTONIN AND CAMP - IMPLICATIONS FOR SPIKE BROADENING

To study the contribution of cAMP to the spike broadening produced by serotonin (5-HT) in the pleural sensory neurons of the tail withdrawal reflex, we utilized two phosphodiesterase-resistant cAMP analogs: the S(P) diastereomer of cyclic adenosine 3',5'-monophosphothioate (S(P)-cAMP[S]), which activates protein kinase A, and the antagonist R(P) diastereomer of cyclic adenosine 3',5'-monophosphothioate (R(P)-cAMP[S]), which is a competitive inhibitor of kinase A. When the cAMP agonist S(P)-cAMP[S] was injected into the sensory neurons, it caused spike broadening comparable to that induced by 5-HT. In turn, the cAMP antagonist R(P)-cAMP[S] blocked almost-equal-to 50% of the 5-HT-induced spike broadening. We next examined the K+ currents that are modulated by 5-HT and determined how these currents are affected by cAMP. Confirming Baxter and Byrne [(1989) J. Neurophysiol. 62, 665-679], we found that 5-HT modulated two currents, an S-type K+ current (I(KS)) as well as a transient and voltage-dependent K+ current (I(KV)). R(P)-cAMP[S] blocked the reduction by 5-HT of the early phase of I(KV) in parallel with, and to the same degree (60%), as this inhibitor blocked the I(KS) and spike broadening. These results support the idea that in the pleural sensory neurons cAMP mediates a significant part of the spike broadening that accompanies short-term facilitation produced by 5-HT and that cAMP can produce spike broadening by modulating both I(KV) and I(KS).