| Excitatory neuromuscular transmission in insects is mediated by glutamate and modulated by various cotransmitters and neurohormones. I have investigated the mechanisms underlying synaptic modulation by the cotransmitter protolin and the neurohormone octopamine in body wall muscles of the larval house fly. High frequency stimulation of the motor neuron or exogenous application of proctolin leads to the appearance of Ca{dollar}sp{lcub}+2{rcub}{dollar} action potentials in the muscle cell. In addition, the peptide causes depolarization of the resting potential (E{dollar}sb{lcub}rm m{rcub}{dollar}), increased input resistance (R{dollar}sb{lcub}rm in{rcub}{dollar}), and enhancement of twitch tension in single muscle cell targets. These actions are associated with enhanced inward barium current and decreased resting K{dollar}sp+{dollar} conductance in muscle targets.; Proctolin actions on Ca{dollar}sp{lcub}+2{rcub}{dollar} action potentials and I{dollar}sb{lcub}rm Ba{rcub}{dollar} are mimicked by the dihydropyridine Ca{dollar}sp{lcub}+2{rcub}{dollar} channel agonist Bay K 8644 and antagonized by nifedipine, verapamil, D600 and diltiazem. This pharmacology suggests activation of L-type voltage sensitive calcium channels (VSCC) by proctolin.; Octopamine modulates muscle excitability by mechanisms that are both similar and distinct from those associated with proctolin. As observed in the proctolin studies, octopamine also leads to activation of VSCC as shown by induction of Ca{dollar}sp{lcub}+2{rcub}{dollar} action potentials and enhancement of I{dollar}sb{lcub}rm Ba{rcub}{dollar} under voltage clamp conditions. In contrast to proctolin, whose actions are strictly postsynaptic, octopamine has potentiating effects on transmitter release. Additional effects of octopamine on larval muscles include induction of a concentration-dependent, biphasic E{dollar}sb{lcub}rm m{rcub}{dollar} response that is associated with increased membrane conductance, g{dollar}sb{lcub}rm m{rcub}{dollar}, and a prolonged increase in gap junctional conductances between adjacent muscle segments.; While octopamine actions on g{dollar}sb{lcub}rm m{rcub}{dollar} and E{dollar}sb{lcub}rm m{rcub}{dollar} responses are mimicked by agents that activate cAMP cascades, amine effects on transmitter release occur in presence of H-89, a selective protein kinase A (PKA) inhibitor, and H-7, a broad spectrum protein kinase inhibitor, suggesting that cAMP and presumably protein kinase C (PKC) are not involved in amine-induced transmitter release. However, H-7 blocks octopamine-induced action potentials suggesting involvement of a protein kinase in the biochemical cascade underlying VSCC activation.; The modulatory properties of proctolin and octopamine through activation of VSCC and electrical coupling between adjacent muscle segments, may facilitate muscle performance and coordination during locomotory behaviours. |
