Table 1.

Nitrergic modulation of ion channels

Channel	Nature of modulation by NO	Impact on cellular response	Ref
Kv1
Kv1.1– 1.6	Current suppression via cGMP-dependent and S-nitrosylation dependent mechanisms	Membrane depolarization, increased excitability	[29,30]
Kv2
Kv2.1	Current suppression in hippocampal CA1 pyramidal neurons via S-nitrosylation	AP widening and reduced firing rates during trains of activity	[32]
Kv2.2	Enhanced currents following long-term NO exposure in principal neurons of the mouse MNTB	Increases firing fidelity allowing high frequency AP trains	[33]
Kv3
Kv3.1/3.2	cGMP-dependent block of currents in CHO cells (Kv3.1/3.2) and mouse MNTB principal neurons (Kv3.1)	Prolonged AP waveforms and reduced AP firing in MNTB neurons	[33,36,37]
Kv4/A-type	Redox-sensitive current suppression via cysteine S-nitrosylation	Increase in neuronal excitability with enhanced spontaneous activity	[40]
Kv7/M-current	Suppression of currents, inhibition of endogenous NOS activity enhances currents	Current inhibition leads to increased excitability in nociceptive neurons	[42]
SK channel	Intrinsic NO production suppresses SK currents in B5 neurons from the buccal ganglion	Leads to membrane depolarization enhanced excitability	[43,44]
BK channel	Current enhancement in CA1 pyramidal hippocampal neurons via S-nitrosylation and in smooth muscle via cGMP/PKG-mediated phosphorylation, Current inhibition in B5 neurons from the buccal ganglion	Enhanced AP repolarization in neurons and muscles	[44,46,47]
Voltage-gated Na+ channel	Suppression of current via a cGMP-dependent and a redox-sensitive component in hippocampal CA1 pyramidal and DRG neurons	Reduced rising phase of single AP depolarization and amplitudes resulting in lower firing frequencies due to limited channel availability	[32,49]
Persistent Na+ channel	Activation of currents in B5 neurons of the buccal ganglion of Helisoma trivolvis, in cultured hippocampal CA1 neurons and Kenyon cells isolated from cricket mushroom bodies; Current suppression in DRG neurons in a cGMP-independent manner	Induces membrane depolarization and increases excitability; Leading to membrane hyperpolarisation to reduce excitability	[43,49,51]
HCN (Ih current)	Activation of currents via cGMP signaling in many neuronal populations; cGMP-independent suppression of currents in magnocellular neurosecretory cells and hypoglossal motoneurons is mediated by S-nitrosylation	Reduction in membrane resistance suppresses the impact of synaptic currents on membrane potential changes; Reduces firing fidelity within trains of APs	[55–57]
VGCC
L- type	Potentiation of currents in mouse principal MNTB neurons, rat hippocampal and cortical neurons; cGMP-dependent current suppression in frog and rat hairs cells	Enhanced calcium influx; Reduced calcium influx	[55,56,59,61,62]
P/Q-type	Potentiation of currents via cGMP signaling in mouse principal MNTB neurons and BHK cells	Enhanced calcium influx	[61,64]
N-type	Current suppression mediated by cGMP signaling in neuroblastoma cells	Reduced calcium influx	[63]
T-Type	Current suppression in rat retinal ganglion neurons by cGMP/PKG signaling and in reticular thalamic nucleus and DRG neurons via a redox-sensitive mechanism (S-nitrosylation)	Reduced calcium influx leading to diminished amplitudes of low-threshold calcium spikes and frequency of spike firing	[65–67]
ATP-sensitive K+ channels	Channel activation in DRG neuron cell-free patches, independent of cGMP signaling but redox-sensitive, cGMP-dependent activation in whole cell recordings from DRG neurons	Modulatory outcomes of KATP channel activation affect neuronal excitability, reduction of excitability in DRG and hippocampal pyramidal neurons	[76–78]
NMDAR	NR1 and NR2A subunit inhibition via S-nitrosylation	Reduction in calcium influx resulting in limited excitotoxicity	[80–82]
AMPAR	S-nitrosylation of N-ethylmaleimide-sensitive factor modulates AMPAR GluR2 surface expression, Direct GluA1 subunit S-nitrosylation	Enhanced GluR2 surface expression leads to stronger postsynaptic excitation; Increased AMPAR GluA1 conductance which facilitates its phosphorylation and reduced surface expression, thereby limiting overall receptor activities and impair LTP/LTD	[85–87]
GABAR	S-nitrosylation of gephyrin, modulates postsynaptic GABAAR clustering, Direct S-nitrosylation of two different Cys residues of GABACR expressed in oocytes	Reduction of receptor clustering reduces inhibitory function of GABA signaling; Enhanced GABA responses increase inhibitory GABAergic function	[88–90]