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 ≈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.