title: Cell-specific regulation of neuronal activity by endogenous production of nitric oxide.
abstract: Nitric oxide (NO) is a key regulator of neuronal excitability in the nervous system. While most studies have investigated its role as an intercellular messenger/modulator, less is known about potential physiological roles played by NO within NO-producing neurons. We showed previously that intrinsic production of NO within B5 neurons of the pond snail Helisoma trivolvis increased neuronal excitability by acting on three ionic conductances. Here we demonstrate that intrinsically produced NO affected two of the same conductances in another buccal neuron, B19, where it had the opposite, namely inhibitory, effect on neuronal activity. Using single-cell RT-PCR, we show that B19 neurons express NO synthase (NOS) mRNA. The inhibition of intrinsic NO production with NOS inhibitors caused membrane potential depolarization, transient spiking and an increase in input resistance. Inhibition of the main intracellular receptor of NO, soluble guanylyl cyclase, had similar effects on the parameters mentioned above. An investigation of the effects of NO on ion channels revealed that intrinsic NO mediated neuronal hyperpolarization by activating voltage-gated calcium channels that in turn caused the tonic opening of apamin-sensitive calcium-activated potassium channels. The analysis of action potentials in B5 and B19 neurons suggested that the opposite effects on neuronal excitability elicited by intrinsic NO were probably determined by differences in the ionic conductances that shape their action potentials. In summary, we describe a mechanism by which B19 neurons utilise intrinsically produced NO in a cell-type-specific fashion to decrease their neuronal activity, highlighting an important physiological role of NO within NO-producing neurons.
authors: Biology Department, Georgia State University, Atlanta, GA, 30302, USA.
authors: Lei Ray
authors: LR
authors: Zhong
authors: Stephen
authors: S
authors: Estes
authors: Liana
authors: L
authors: Artinian
authors: Vincent
authors: V
authors: Rehder
mesh_terms: D000200:Action Potentials; D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D002478:Cells, Cultured; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D012908:Snails
chemical_list: D015220:Calcium Channels; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase
keywords: Helisoma trivolvis; NO synthase; SK channel; calcium channel; sGC