Voltage-Gated Ion Channels in Nociceptors: Modulation by cGMP

2004 ◽  
Vol 92 (4) ◽  
pp. 2323-2332 ◽  
Author(s):  
L. Liu ◽  
T. Yang ◽  
M. J. Bruno ◽  
O. S. Andersen ◽  
S. A. Simon
Keyword(s):  
Ion Channels ◽  
Delayed Rectifier ◽  
Channel Activity ◽  
Nociceptive Neurons ◽  
Voltage Gated ◽  
Channel Function ◽  
Proinflammatory Mediators ◽  
Whole Cell Patch Clamp ◽  
Voltage Gated Ion Channels ◽  
Ganglion Neurons

In tissue or nerve injury, proinflammatory mediators are released that can modulate a variety of ion channels found in nociceptors. The changes in channel activity, which primarily occurs through changes in intracellular pathways, may lead to the pathological states of hyperalgesia and allodynia. To understand further the regulatory mechanisms underlying the changes in channel activity, we used whole cell patch-clamp recordings from capsaicin-sensitive nociceptive neurons in rat trigeminal ganglion neurons to examine how the cGMP-dependent pathways may regulate ion channel function. Addition of the 8-(4-chlorophenylthio)-3′,5′ (CPT)-cGMP, a membrane permeant modulator of ion channels, decreased the number of evoked action potentials by 36% and inhibited the tetrodotoxin-resistant (TTX-R) sodium currents and IA potassium currents by 37 and 32%, respectively. Delayed rectifier potassium ( IK) currents were unaffected, suggesting that the effects of CPT-cGMP are unlikely to arise from a nonspecific effect on channel activity as a consequence of the adsorption of amphipathic CPT-cGMP molecules to the membrane's bilayer component. This conclusion was reinforced by the lack of changes in gramicidin A channel function in the presence of CTP-cGMP. In summary, the activation of the cGMP-dependent pathways reduces nociceptor excitability, in part, by decreasing the activity of voltage-gated TTX-R sodium channels. This pathway may be a target for efforts to produce selective analgesics.

scholarly journals Fluorescence Imaging of Electrically Stimulated Cells

2003 ◽  
Vol 8 (6) ◽  
pp. 660-667 ◽  
Author(s):  
Paul Burnett ◽  
Janet K. Robertson ◽  
Jeffrey M. Palmer ◽  
Richard R. Ryan ◽  
Adrienne E. Dubin ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Ion Channels ◽  
Ion Channel ◽  
High Throughput ◽  
Pharmacological Intervention ◽  
Voltage Gradient ◽  
Channel Activity ◽  
Voltage Gated ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

Designing high-throughput screens for voltage-gated ion channels has been a tremendous challenge for the pharmaceutical industry because channel activity is dependent on the transmembrane voltage gradient, a stimulus unlike ligand binding to G-protein-coupled receptors or ligand-gated ion channels. To achieve an acceptable throughput, assays to screen for voltage-gated ion channel modulators that are employed today rely on pharmacological intervention to activate these channels. These interventions can introduce artifacts. Ideally, a high-throughput screen should not compromise physiological relevance. Hence, a more appropriate method would activate voltage-gated ion channels by altering plasma membrane potential directly, via electrical stimulation, while simultaneously recordingthe operation of the channel in populations of cells. The authors present preliminary results obtained from a device that is designed to supply precise and reproducible electrical stimuli to populations of cells. Changes in voltage-gated ion channel activity were monitored using a digital fluorescent microscope. The prototype electric field stimulation (EFS) device provided real-time analysis of cellular responsiveness to physiological and pharmacological stimuli. Voltage stimuli applied to SK-N-SH neuroblastoma cells cultured on the EFS device evoked membrane potential changes that were dependent on activation of voltage-gated sodium channels. Data obtained using digital fluorescence microscopy suggests suitability of this system for HTS.

Zinc and Copper Influence Excitability of Rat Olfactory Bulb Neurons by Multiple Mechanisms

2001 ◽  
Vol 86 (4) ◽  
pp. 1652-1660 ◽  
Author(s):  
Michelle S. Horning ◽  
Paul Q. Trombley
Keyword(s):  
Ion Channels ◽  
Potassium Channels ◽  
Olfactory Bulb ◽  
Membrane Potentials ◽  
Repetitive Firing ◽  
Delayed Rectifier ◽  
Voltage Gated ◽  
Voltage Gated Ion Channels ◽  
Olfactory Bulb Neurons ◽  
Gated Ion Channels

Zinc and copper are highly concentrated in several mammalian brain regions, including the olfactory bulb and hippocampus. Whole cell electrophysiological recordings were made from rat olfactory bulb neurons in primary culture to compare the effects of zinc and copper on synaptic transmission and voltage-gated ion channels. Application of either zinc or copper eliminated GABA-mediated spontaneous inhibitory postsynaptic potentials. However, in contrast to the similarity of their effects on inhibitory transmission, spontaneous glutamate-mediated excitatory synaptic activity was completely blocked by copper but only inhibited by zinc. Among voltage-gated ion channels, zinc or copper inhibited TTX-sensitive sodium channels and delayed rectifier-type potassium channels but did not prevent the firing of evoked single action potentials or dramatically alter their kinetics. Zinc and copper had distinct effects on transient A-type potassium currents. Whereas copper only inhibited the A-type current, zinc modulation of A-type currents resulted in either potentiation or inhibition of the current depending on the membrane potential. The effects of zinc and copper on potassium channels likely underlie their effects on repetitive firing in response to long-duration step depolarizations. Copper reduced repetitive firing independent of the initial membrane voltage. In contrast, whereas zinc reduced repetitive firing at membrane potentials associated with zinc-mediated enhancement of the A-type current (−50 mV), in a significant proportion of neurons, zinc increased repetitive firing at membrane potentials associated with zinc-mediated inhibition of the A-type current (−90 mV). Application of zinc or copper also inhibited voltage-gated Ca2+ channels, suggesting a possible role for presynaptic modulation of neurotransmitter release. Despite similarities between the effects of zinc and copper on some ligand- and voltage-gated ion channels, these data suggest that their net effects likely contribute to differential modulation of neuronal excitability.

scholarly journals A mathematical investigation of chemotherapy-induced peripheral neuropathy

2020 ◽  
Author(s):  
Parul Verma ◽  
Muriel Eaton ◽  
Achim Kienle ◽  
Dietrich Flockerzi ◽  
Yang Yang ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Ion Channels ◽  
Bifurcation Analysis ◽  
Electrode Array ◽  
Delayed Rectifier ◽  
Voltage Gated ◽  
Mathematical Investigation ◽  
Voltage Gated Ion Channels ◽  
Multi Electrode Array ◽  
Gated Ion Channels

AbstractChemotherapy-induced peripheral neuropathy (CIPN) is a prevalent, painful side effect which arises due to a number of chemotherapy agents. CIPN can have a prolonged effect on quality of life. Chemotherapy treatment is often reduced or stopped altogether because of the severe pain. Currently, there are no FDA-approved treatments for CIPN partially due to its complex pathogenesis in multiple pathways involving a variety of channels, specifically, voltage-gated ion channels. A surrogate of neuropathic pain in an in vitro setting is hyperexcitability in dorsal root ganglia (DRG) peripheral sensory neurons. Our study employs bifurcation theory to investigate the role of voltage-gated ion channels in inducing hyperexcitability as a consequence of spontaneous firing, due to the common chemotherapy agent paclitaxel. Our mathematical investigation suggests that the sodium channel Nav1.8 and the delayed rectifier potassium channel conductances are the most critical for hyperexcitability in normal firing small DRG neurons. Introducing paclitaxel into the model, our bifurcation analysis predicts that hyperexcitability is extreme for a medium dose of paclitaxel, which is validated by multi-electrode array recordings. Our findings using multi-electrode array experiments reveal that the Nav1.8 blocker A-803467 and the delayed rectifier potassium enhancer L-alpha-phosphatidyl-D-myo-inositol 4,5-diphosphate, dioctanoyl (PIP2) have a protective effect on the firing rate of DRG when administered separately together with paclitaxel as suggested by our bifurcation analysis.

scholarly journals The estrous cycle modulates voltage-gated ion channels in trigeminal ganglion neurons

2015 ◽  
Vol 65 (S2) ◽  
pp. S29-S35
Author(s):  
Wachirapong Saleeon ◽  
Ukkrit Jansri ◽  
Anan Srikiatkhachorn ◽  
Saknan Bongsebandhu-phubhakdi
Keyword(s):  
Ion Channels ◽  
Estrous Cycle ◽  
Trigeminal Ganglion ◽  
Voltage Gated ◽  
Trigeminal Ganglion Neurons ◽  
Voltage Gated Ion Channels ◽  
Ganglion Neurons ◽  
Gated Ion Channels

scholarly journals Activity of Palythoa caribaeorum Venom on Voltage-Gated Ion Channels in Mammalian Superior Cervical Ganglion Neurons

Toxins ◽  
2016 ◽  
Vol 8 (5) ◽  
pp. 135 ◽  
Author(s):  
Fernando Lazcano-Pérez ◽  
Héctor Castro ◽  
Isabel Arenas ◽  
David García ◽  
Ricardo González-Muñoz ◽  
...  
Keyword(s):  
Ion Channels ◽  
Superior Cervical Ganglion ◽  
Voltage Gated ◽  
Palythoa Caribaeorum ◽  
Cervical Ganglion ◽  
Voltage Gated Ion Channels ◽  
Ganglion Neurons ◽  
Gated Ion Channels

scholarly journals Hysteretic Behavior in Voltage-Gated Channels

2020 ◽  
Vol 11 ◽  
Author(s):  
Carlos A. Villalba-Galea ◽  
Alvin T. Chiem
Keyword(s):  
Ion Channels ◽  
Hysteretic Behavior ◽  
Channel Activity ◽  
Apparent Contradiction ◽  
Molecular Systems ◽  
Voltage Gated ◽  
Hysteretic Systems ◽  
Gated Channel ◽  
Voltage Gated Channels ◽  
Voltage Gated Ion Channels

An ever-growing body of evidence has shown that voltage-gated ion channels are likely molecular systems that display hysteresis in their activity. This phenomenon manifests in the form of dynamic changes in both their voltage dependence of activity and their deactivation kinetics. The goal of this review is to provide a clear definition of hysteresis in terms of the behavior of voltage-gated channels. This review will discuss the basic behavior of voltage-gated channel activity and how they make these proteins into systems displaying hysteresis. It will also provide a perspective on putative mechanisms underlying hysteresis and explain its potential physiological relevance. It is uncertain whether all channels display hysteresis in their behavior. However, the suggested notion that ion channels are hysteretic systems directly collides with the well-accepted notion that ion channel activity is stochastic. This is because hysteretic systems are regarded to have “memory” of previous events while stochastic processes are regarded as “memoryless.” This review will address this apparent contradiction, providing arguments for the existence of processes that can be simultaneously hysteretic and stochastic.

Voltage-Gated Ion Channels, New Targets in Anti-Cancer Research

2007 ◽  
Vol 2 (3) ◽  
pp. 189-202 ◽  
Author(s):  
Le Jean-Yves ◽  
Ouadid-Ahidouch Halima ◽  
Soriani Olivier ◽  
Besson Pierre ◽  
Ahidouch Ahmed ◽  
...  
Keyword(s):  
Cancer Research ◽  
Ion Channels ◽  
Voltage Gated ◽  
New Targets ◽  
Anti Cancer ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels
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