title: Nitric oxide and histamine induce neuronal excitability by blocking background currents in neuron MCC of Aplysia.
abstract: Nitric oxide (NO) and histamine are important neurotransmitters and neuromodulators. We investigated their ability to modulate the membrane ionic currents and excitability of the metacerebral cell (MCC) of Aplysia using voltage clamp techniques. MCC is a serotonergic modulator of the feeding neural circuit. It receives powerful long-lasting excitatory synaptic input mediated by NO and histamine. NO donors reduced a background outward current at and above the resting potential, associated with decreased membrane conductance. This produced a substantial steady-state inward current that was relatively insensitive to cesium or cobalt. The NO response appears to be due to the reduction of a background potassium current and a small increase in persistent inward sodium current. Treatment with 8-bromoguanosine-3'5'-cyclic monophosphate mimics this response, suggesting it is mediated primarily by the NO-guanylyl cyclase-cGMP pathway. In some MCCs, NO blocked an additional potassium current that resulted in current reversal near the potassium equilibrium potential in current-voltage plots. Histamine also reduced a background outward current at and above the resting potential. However, treatment with cobalt, which blocks calcium and calcium-dependent currents, blocked the histamine response, suggesting that histamine decreases calcium activated potassium currents. Although nifedipine (L-type calcium channel blocker) and tetraethylammonium reduced some calcium and calcium-dependent potassium currents, they had only a slight effect on the NO and histamine responses. Both NO and histamine decreased steady-state membrane currents, and thereby depolarized MCC and increased its excitability, but different ionic currents and second messenger pathways are involved, allowing complex state and time dependent modulation of MCC's activity.
authors.affiliation: Department of Biological Sciences, University at Albany, State University of New York, Albany, New York 12222, USA. jwj74@albany.edu
authors.forename: Jon W
authors.initials: JW
authors.lastname: Jacklet
authors.forename: David G
authors.initials: DG
authors.lastname: Tieman
mesh_terms: D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001048:Aplysia / Q000187:drug effects* / Q000502:physiology; D006632:Histamine / Q000494:pharmacology* / Q000502:physiology; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology
chemical_list: D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D006632:Histamine