title: Activators of protein kinase C mimic serotonin-induced modulation of a voltage-dependent potassium current in pleural sensory neurons of Aplysia.
abstract: 1. In the pleural mechanoafferent sensory neurons of Aplysia, serotonin (5-HT)-induced spike broadening consists of at least two components: a cAMP and protein kinase A (PKA)-dependent, rapidly developing component and a protein kinase C (PKC)-dependent, slowly developing component. Voltage-clamp experiments were conducted to identify currents that are modulated by PKC and thus may contribute to the slowly developing component of 5-HT-induced spike broadening. 2. We compared the effects of phorbol esters, activators of PKC, on membrane currents with those of 5-HT. Bath application of 5-HT had complex modulatory effects on currents elicited by voltage-clamp pulses to potentials > 0 mV. The kinetics of both activation and inactivation of the membrane currents were slowed by 5-HT. This led to a decrease in an outward current at the beginning of the voltage-clamp pulse and an increase at the end of the pulse. Previous work has shown that these effects represent, in part, the modulation of a large, voltage-dependent K+ current (IK,V) by 5-HT. 3. Active phorbol esters mimicked some of the actions of 5-HT on membrane currents in that they slowed activation and inactivation kinetics of current responses to voltage-clamp pulses more positive than 0 mV. This led to a decrease in an outward current at the beginning of the pulse and an increase at the end of the pulse. Because inactive phorbols did not mimic the actions of 5-HT, the effects of active phorbol esters appeared to be PKC specific. In addition, preexposure of the sensory neurons to active phorbol esters appeared to occlude the modulatory actions of 5-HT on IK,V. Thus it is likely that modulation of IK,V by 5-HT is mediated, at lease in part, by PKC. 4. To further characterize which currents were modulated by PKC, low concentrations of tetraethylammonium (TEA, 2 mM) were used to block Ca(2+)-activated K+ current (IK,Ca). Low TEA partially blocked the phorbol ester-induced increase of the outward current at the end of voltage-clamp pulses. These results agreed with previous reports that activation of PKC enhanced a fast component of IK,Ca in these sensory neurons. Such an enhancement would lead to an increase in outward current that should be blocked by low TEA. Low TEA, however, did not affect phorbol ester-induced decrease of the outward current at the beginning of pulse, where the predominant current is IK,V, which is less sensitive to TEA.(ABSTRACT TRUNCATED AT 400 WORDS)
authors: Department of Neurobiology and Anatomy, University of Texas Medical School at Houston 77225.
authors: S
authors: S
authors: Sugita
authors: D A
authors: DA
authors: Baxter
authors: J H
authors: JH
authors: Byrne
mesh_terms: D000818:Animals; D001048:Aplysia; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D046508:Culture Techniques; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D017952:Ganglia, Invertebrate / Q000187:drug effects* / Q000502:physiology; D008465:Mechanoreceptors / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D010703:Phorbol Esters / Q000494:pharmacology; D010994:Pleura / Q000294:innervation; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D010703:Phorbol Esters; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D012701:Serotonin; D019789:Tetraethylammonium; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C