The Impact of Ancillary Subunits on Small-Molecule Interactions with Voltage-Gated Potassium Channels

This review describes the synthetic and medicinal chemistry of small molecule modulators of the voltage-gated Kv7 (KCNQ) potassium channels and the available data of their biological and clinical properties.

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Potassium channels contribute to activity-dependent scaling of dendritic inhibition

10.1101/098889 ◽

2017 ◽

Author(s):

Jeremy T. Chang ◽

Michael J. Higley

Keyword(s):

Potassium Channels ◽

Neuronal Activity ◽

Neuronal Excitability ◽

Pyramidal Neurons ◽

Critical Role ◽

Pyramidal Cells ◽

Gabaergic Inhibition ◽

Voltage Gated ◽

The Impact ◽

Activity Dependent

AbstractGABAergic inhibition plays a critical role in the regulation of neuronal activity. In the neocortex, inhibitory interneurons that target the dendrites of pyramidal cells influence both electrical and biochemical postsynaptic signaling. Voltage-gated ion channels strongly shape dendritic excitability and the integration of excitatory inputs, but their contribution to GABAergic signaling is less well understood. By combining 2-photon calcium imaging and focal GABA uncaging, we show that voltage-gated potassium channels normally suppress the GABAergic inhibition of calcium signals evoked by back-propagating action potentials in dendritic spines and shafts of cortical pyramidal neurons. Moreover, the voltage-dependent inactivation of these channels leads to enhancement of dendritic calcium inhibition following somatic spiking. Computational modeling reveals that the enhancement of calcium inhibition involves an increase in action potential depolarization coupled with the nonlinear relationship between membrane voltage and calcium channel activation. Overall, our findings highlight the interaction between intrinsic and synaptic properties and reveal a novel mechanism for the activity-dependent scaling of GABAergic inhibition.Significance StatementGABAergic inhibition potently regulates neuronal activity in the neocortex. How such inhibition interacts with the intrinsic electrophysiological properties of single neurons is not well-understood. Here we investigate the ability of voltage-gated potassium channels to regulate the impact of GABAergic inhibition in the dendrites of neocortical pyramidal neurons. Our results show that potassium channels normally reduce inhibition directed towards pyramidal neuron dendrites. However, these channels are inactivated by strong neuronal activity, leading to an enhancement of GABAergic potency and limiting the corresponding influx of dendritic calcium. Our findings illustrate a previously unappreciated relationship between neuronal excitability and GABAergic inhibition.

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Faculty Opinions recommendation of Enzymatic activation of voltage-gated potassium channels.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.14682.472197 ◽

2006 ◽

Author(s):

Ole Skøtt

Keyword(s):

Potassium Channels ◽

Voltage Gated ◽

Enzymatic Activation

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Faculty Opinions recommendation of Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718204795.793488513 ◽

2013 ◽

Author(s):

Francisco Bezanilla ◽

Jerome Lacroix

Keyword(s):

Potassium Channels ◽

Hydrogen Bonds ◽

Slow Inactivation ◽

Voltage Gated

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Voltage-gated potassium channels and trigeminal neuralgia

Academic Journal of Second Military Medical University ◽

10.3724/sp.j.1008.2009.00432 ◽

2009 ◽

Vol 29 (4) ◽

pp. 432-436

Author(s):

Na LI ◽

Bei MA ◽

Xiao-ming DENG

Keyword(s):

Potassium Channels ◽

Trigeminal Neuralgia ◽

Voltage Gated

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Roles of Microglial Ion Channel in Neurodegenerative Diseases

Journal of Clinical Medicine ◽

10.3390/jcm10061239 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1239

Author(s):

Alexandru Cojocaru ◽

Emilia Burada ◽

Adrian-Tudor Bălșeanu ◽

Alexandru-Florian Deftu ◽

Bogdan Cătălin ◽

...

Keyword(s):

Ion Channels ◽

Neurodegenerative Diseases ◽

Excitable Cells ◽

Proton Channels ◽

Voltage Gated ◽

Cellular Processes ◽

Pathological Conditions ◽

The Common ◽

Transient Receptor ◽

The Impact

As the average age and life expectancy increases, the incidence of both acute and chronic central nervous system (CNS) pathologies will increase. Understanding mechanisms underlying neuroinflammation as the common feature of any neurodegenerative pathology, we can exploit the pharmacology of cell specific ion channels to improve the outcome of many CNS diseases. As the main cellular player of neuroinflammation, microglia play a central role in this process. Although microglia are considered non-excitable cells, they express a variety of ion channels under both physiological and pathological conditions that seem to be involved in a plethora of cellular processes. Here, we discuss the impact of modulating microglia voltage-gated, potential transient receptor, chloride and proton channels on microglial proliferation, migration, and phagocytosis in neurodegenerative diseases.

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Presynaptic Paraneoplastic Disorders of the Neuromuscular Junction: An Update

Brain Sciences ◽

10.3390/brainsci11081035 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1035

Author(s):

Maria Pia Giannoccaro ◽

Patrizia Avoni ◽

Rocco Liguori

Keyword(s):

Potassium Channels ◽

Neuromuscular Junction ◽

Calcium Channels ◽

Myasthenia Gravis ◽

Neuromuscular Transmission ◽

Voltage Gated ◽

Voltage Gated Calcium Channels ◽

Immune Mediated ◽

Recent Developments ◽

Myasthenic Syndrome

The neuromuscular junction (NMJ) is the target of a variety of immune-mediated disorders, usually classified as presynaptic and postsynaptic, according to the site of the antigenic target and consequently of the neuromuscular transmission alteration. Although less common than the classical autoimmune postsynaptic myasthenia gravis, presynaptic disorders are important to recognize due to the frequent association with cancer. Lambert Eaton myasthenic syndrome is due to a presynaptic failure to release acetylcholine, caused by antibodies to the presynaptic voltage-gated calcium channels. Acquired neuromyotonia is a condition characterized by nerve hyperexcitability often due to the presence of antibodies against proteins associated with voltage-gated potassium channels. This review will focus on the recent developments in the autoimmune presynaptic disorders of the NMJ.

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