The Journal of Neurophysiology Vol. 82 No. 2 August 1999, pp. 626-637
Copyright ©1999 by the American Physiological Society

Serotonergic Modulation of the Hyperpolarizing Spike Afterpotential in Rat Jaw-Closing Motoneurons by PKA and PKC

Departments of  ¹Oral Physiology,  ²Orthodontics, and  ³Oral Anatomy, Faculty of Dentistry, Osaka University, Osaka 565-0871; and  ⁴Department of Physiology, Faculty of Medicine, Kyoto University, Kyoto 606-8315, Japan

Inoue, Tomio, Satsuki Itoh, Masayuki Kobayashi, Youngnam Kang, Ryuji Matsuo, Satoshi Wakisaka, and Toshifumi Morimoto. Serotonergic Modulation of the Hyperpolarizing Spike Afterpotential in Rat Jaw-Closing Motoneurons by PKA and PKC. J. Neurophysiol. 82: 626-637, 1999. Intracellular recordings were obtained from rat jaw-closing motoneurons (JCMNs) in slice preparations to investigate the effects of serotonin (5-HT) on the postspike medium-duration afterhyperpolarization (mAHP) and an involvement of protein kinases in the effects. Application of 50 µM 5-HT caused membrane depolarization and increased input resistance in the most cells without affecting the mAHP, whereas not only membrane depolarization and an increase in input resistance, but also the suppression of the mAHP amplitude was induced by higher dose of 5-HT (100 or 200 µM). On the other hand, when the mAHP amplitude was increased by raising [Ca²⁺]_o from 2 to 6 mM, 5-HT-induced attenuation of the mAHP amplitude was enhanced, and even 50 µM 5-HT reduced the mAHP amplitude. This 5-HT-induced suppression of the mAHP could be mimicked by application of membrane-permeable cAMP analogue 8-Bromo-cAMP, potentiated by the cAMP-specific phosphodiesterase inhibitor Ro 20-1724 and antagonized by protein kinase A (PKA) inhibitor H89. The enhancement of the mAHP attenuation induced by 50 µM 5-HT under raised [Ca²⁺]_o was blocked by a protein kinase C (PKC) inhibitor chelerythrine, suggesting an involvement of PKC in this enhancement. On the other hand, the attenuation of the mAHP induced by PKC activator phorbol 12-myristate 13-acetate was blocked almost completely by H89, suggesting that the PKC action on the mAHP requires PKA activation. Neither 5-HT_1A antagonist NAN-190 or 5-HT₄ antagonist SB 203186 blocked 5-HT-induced attenuation of the mAHP. We conclude that 5-HT induces dose-dependent attenuation of the mAHP amplitude through cAMP-dependent activation of PKA and that PKC-dependent PKA activation is also likely to be involved in the enhancement of 5-HT-induced attenuation of the mAHP under raised [Ca²⁺]_o. Because the slope of the linear relationship between firing frequency and injected current was increased only when the mAHP amplitude was decreased by 5-HT, it is suggested that the relation between incoming synaptic inputs and firing output in JCMNs varies according to serotonergic effects on JCMNs and calcium-dependent modulation of its effects.