Abstract
Nitric oxide (NO) is an unconventional membrane-permeable messenger molecule that has been shown to play various roles in the nervous system. How NO modulates ion channels to affect neuronal functions is not well understood. In gastropods, NO has been implicated in regulating the feeding motor program. The buccal motoneuron, B19, of the freshwater pond snail Helisoma trivolvis is active during the hyper-retraction phase of the feeding motor program and is located in the vicinity of NO-producing neurons in the buccal ganglion. Here, we asked whether B19 neurons might serve as direct targets of NO signaling. Previous work established NO as a key regulator of growth cone motility and neuronal excitability in another buccal neuron involved in feeding, the B5 neuron. This raised the question whether NO might modulate the electrical activity and neuronal excitability of B19 neurons as well, and if so whether NO acted on the same or a different set of ion channels in both neurons. To study specific responses of NO on B19 neurons and to eliminate indirect effects contributed by other cells, the majority of experiments were performed on single cultured B19 neurons. Addition of NO donors caused a prolonged depolarization of the membrane potential and an increase in neuronal excitability. The effects of NO could mainly be attributed to the inhibition of two types of calcium-activated potassium channels, apamin-sensitive and iberiotoxin-sensitive potassium channels. NO was found to also cause a depolarization in B19 neurons in situ, but only after NO synthase activity in buccal ganglia had been blocked. The results suggest that NO acts as a critical modulator of neuronal excitability in B19 neurons, and that calcium-activated potassium channels may serve as a common target of NO in neurons.
Highlights
Nitric oxide (NO) serves as an unconventional membranepermeable messenger molecule in the nervous systems of vertebrates and invertebrates, where it has been implicated in various cellular processes, including neuronal migration [1], synaptogenesis [2], long-term potentiation [3], and memory formation [4,5]
We found that NO donors caused a prolonged depolarization of the membrane potential and an increase in neuronal excitability in cultured B19 neurons
Isolated B19 neurons from the buccal ganglion of Helisoma trivolvis were used for whole-cell patch-clamp experiments 24– 48 hour after plating, at which time all neurons had welldeveloped neurites with growth cones at their tips. 74.6 percent of B19 neurons recorded (44 out of 59) were silent with a resting membrane potential at 241.260.7 mV, whereas the rest of B19 neurons (25.4%, 15 out of 59) fired spontaneous action potentials (APs) and had a slightly more depolarized membrane potential of 238.360.7 mV (P,0.05; Two-sample t-test)
Summary
Nitric oxide (NO) serves as an unconventional membranepermeable messenger molecule in the nervous systems of vertebrates and invertebrates, where it has been implicated in various cellular processes, including neuronal migration [1], synaptogenesis [2], long-term potentiation [3], and memory formation [4,5]. How NO modulates membrane channels to affect aspects of the functional output of neuronal circuits is of central interest in many systems. Using isolated neurons from the buccal ganglion of Helisoma trivolvis, NO has been characterized as a regulator of neurite outgrowth and growth cone motility [11,12]. Application of NO-donors to the buccal neuron B5 slowed the advance of growing neurites [13], whereas growth cone filopodia underwent transient elongation [11], suggesting a role for NO in neuronal pathfinding during development and regeneration. NO has been shown to modulate neuronal excitability in B5 neurons by selectively affecting ion channels, such as K+ and Ca2+ channels [14,15]. On the level of neuronal circuitry and animal behavior, NO has been shown to be important in aerial respiration and long-term associative memory in Lymnaea [4,16,17] and in feeding behaviors in Aplysia [18,19,20,21] and Lymnaea [22,23,24]
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