Fine tuning of neuronal electrical activity: modulation of several ion channels by intracellular messengers in a single identified nerve cell.

The identified neurone R15 in the abdominal ganglion of the marine mollusc, Aplysia californica, exhibits a rhythmic bursting pattern of electrical activity. This pattern, which is generated endogenously by the interaction of several voltage- and time-dependent ion currents in R15's membrane, is subject to long-term modulation by synaptic stimulation and application of several neurotransmitters. At micromolar concentrations the transmitter serotonin causes neurone R15 to hyperpolarize, as a result of the activation of an anomalously rectifying potassium conductance. Furthermore under some conditions serotonin can excite R15, as a result of the activation of a voltage-dependent calcium current. Both of these effects of serotonin are mediated by the intracellular second messenger cyclic AMP. In addition, serotonin can modulate a chloride current by a cyclic-AMP-dependent mechanism. In contrast to the activation of the voltage-dependent calcium current by serotonin/cyclic AMP, a cyclic GMP analogue alters the bursting pattern by inhibiting this current. The results indicate that a single neurotransmitter, acting via a single intracellular messenger, can modulate several classes of ion channels in a single nerve cell. Furthermore a single class of ion channel, that is responsible for a voltage-dependent calcium current, may be the target for modulation by at least two different intracellular messengers. These findings emphasize the intricacy of the regulatory pathways which contribute to fine tuning of neuronal electrical activity.