| Frog sympathetic neurons have been widely used as a model system for studying regulation of neuronal excitability. These cells exhibit robust slow synaptic potentials resulting from modulation of ion channels active at resting or weakly depolarized membrane potentials. The M-current, a voltage-dependent K+ current, can be inhibited by actions of endogenous ganglionic transmitters such as acetylcholine (ACh), epinephrine (EPI), luteinizing hormone-releasing hormone (LHRH) or substance P (SP). Decreased K+ conductances, along with an increased leak conductance, play a major role in generating slow excitatory postsynaptic potentials (EPSPs). Any of the endogenous neurotransmitters could affect voltage-gated Ca2+ channels. Effects on Ca 2+ entry might be important in understanding sympathetic physiology.; The effects of LHRH, SP, ACh, and EPI on Ca2+ channels and M- and leak currents of frog sympathetic neurons were studied. LHRH, SP and EPI effectively inhibited N-type Ca2+ currents and M-type K+ currents. The notable exception was ACh, which had little effect on high-voltage activated Ca2+ channels, even when it almost completely blocked the M-current. LHRH also induced a leak conductance. The peptidergic inhibition of Ca2+ channels was mimicked by cytoplasmic GTPγS but not by modulators of protein kinases, consistent with the involvement of a G Protein, but not protein phosphorylation. No evidence for the involvement of intracellular messengers was found.; LHRH decreased Ca2+-activated K+ current, most likely as a consequence of the inhibition of Ca2+ influx. Inhibition of this K+ current would result in prolonged action potentials, reduced afterhyperpolarizations, and increased excitability, in synergy with the effects of M-current suppression. On the other hand, LHRH also decreased transmitter release evoked by K+ depolarization. Thus, modulation of Ca2+ channels plays a prominent role, along with M-current suppression and leak current induction, in the overall regulation of ganglionic function by neurotransmitters. |
