Electrophysiological Roles of L-Type Channels in Different Classes of Guinea Pig Sympathetic Neuron

Abstract

The electrophysiological consequences of blocking Ca2+ entry through L-type Ca2+ channels have been examined in phasic ( Ph), tonic ( T), and long-afterhyperpolarizing ( LAH) neurons of intact guinea pig sympathetic ganglia isolated in vitro. Block of Ca2+entry with Co2+ or Cd2+ depolarized T and LAH neurons, reduced action potential (AP) amplitude in Ph and LAHneurons, and increased AP half-width in Ph neurons. The afterhyperpolarization (AHP) and underlying Ca2+-dependent K+ conductances ( gKCa1 and gKCa2) were reduced markedly in all classes. Addition of 10 μM nifedipine increased input resistance in LAHneurons, raised AP threshold in Ph and LAH neurons, and caused a small increase in AP half-width in Ph neurons. AHP amplitude and the amplitude and decay time constant of gKCa1 were reduced by nifedipine in all classes; the slower conductance, gKCa2, which underlies the prolonged AHP in LAH neurons, was reduced by 40%. Surprisingly, AHP half-width was lengthened by nifedipine in a proportion of neurons in all classes; despite this, neuron excitability was increased during a maintained depolarization. Nifedipine’s effects on AHP half-width were not mimicked by 2 mM Cs+ or 2 mM anthracene-9-carboxylic acid, a blocker of Cl− channels, and it did not modify transient outward currents of the A or D types. The effects of 100 μM Ni2+ differed from those of nifedipine. Thus in Ph neurons, Ca2+ entry through L-type channels during a single action potential contributes to activation of K+ conductances involved in both the AP and AHP, whereas in T and LAH neurons, it acts only on gKCa1 and gKCa2. These results differ from the results in rat superior cervical ganglion neurons, in which L-type channels are selectively coupled to BK channels, and in hippocampal neurons, in which L-type channels are selectively coupled to SK channels. We conclude that the sources of Ca2+ for activating the various Ca2+-activated K+conductances are distinct in different types of neuron.