RT Journal Article
SR Electronic
T1 Serotonin acting via cyclic AMP enhances both the hyperpolarizing and depolarizing phases of bursting pacemaker activity in the Aplysia neuron R15
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1152
OP 1161
DO 10.1523/JNEUROSCI.08-04-01152.1988
VO 8
IS 4
A1 ES Levitan
A1 IB Levitan
YR 1988
UL http://www.jneurosci.org/content/8/4/1152.abstract
AB Bath application of 5-HT, at concentrations below 10 microM, enhances the amplitude of the interburst hyperpolarization in the Aplysia bursting pacemaker neuron R15. It is known that 5-HT acts via cyclic AMP to produce this effect by increasing the inwardly rectifying potassium current (IR). Here, we report that further elevating the concentration of 5-HT produces an enhancement of the depolarizing phase of the burst cycle that can eventually lead to tonic spiking activity. Voltage-clamp studies reveal that high concentrations of 5-HT continue to increase IR and, in addition enhance a voltage-gated inward current active near the action potential threshold. Pharmacological treatments and ion substitution experiments demonstrate that the inward current increased by high concentrations of 5-HT is a subthreshold calcium current (ICa). The 5-HT-induced increase in ICa is mimicked by bath application of the adenylate cyclase activator forskolin or injection of 8-bromo-cyclic AMP and is potentiated by the phosphodiesterase inhibitor isobutylmethylxanthine. It is concluded that 5-HT, acting via the second messenger cyclic AMP, can increase both potassium and calcium currents in neuron R15. It is also shown that the 5-HT-induced increase in these 2 opposing voltage-gated currents not only produces complex changes in bursting activity, but also dramatically alters R15's response to inhibitory and excitatory stimuli.