Nitric oxide acts as a volume transmitter to modulate electrical properties of spontaneously firing neurons via apamin-sensitive potassium channels.
Nitric oxide (NO) is a radical and a gas, properties that allow NO to diffuse through membranes and potentially enable it to function as a "volume messenger." This study had two goals: first, to investigate the mechanisms by which NO functions as a modulator of neuronal excitability, and second, to compare NO effects produced by NO release from chemical NO donors with those elicited by physiological NO release from single neurons. We demonstrate that NO depolarizes the membrane potential of B5 neurons of the mollusk Helisoma trivolvis, initially increasing their firing rate and later causing neuronal silencing. Both effects of NO were mediated by inhibition of Ca-activated iberiotoxin- and apamin-sensitive K channels, but only inhibition of apamin-sensitive K channels fully mimicked all effects of NO on firing activity, suggesting that the majority of electrical effects of NO are mediated via inhibition of apamin-sensitive K channels. We further show that single neurons release sufficient amounts of NO to affect the electrical activity of B5 neurons located nearby. These effects are similar to NO release from the chemical NO donor NOC-7 [3-(2-hydroxy-1-methyl-2-nitrosohydazino)-N-methyl-1-propyanamine], validating the use of NO donors in studies of neuronal excitability. Together with previous findings demonstrating a role for NO in neurite outgrowth and growth cone motility, the results suggest that NO has the potential to shape the development of the nervous system by modulating both electrical activity and neurite outgrowth in neurons located in the vicinity of NO-producing cells, supporting the notion of NO functioning as a volume messenger.
Artinian
Liana
L
Department of Biology, Georgia State University, Atlanta, Georgia 30302-4010, USA.
Tornieri
Karine
K
Zhong
Lei
L
Baro
Deborah
D
Rehder
Vincent
V
D000595:Amino Acid Sequence; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D017952:Ganglia, Invertebrate / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D006834:Hydrazines / Q000494:pharmacology; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000737:chemistry / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D012908:Snails
C115239:3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamine; D015220:Calcium Channels; D006834:Hydrazines; D020030:Nitric Oxide Donors; D015221:Potassium Channels; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase