CaV3.2 calcium channels: new players in facial pain

Gómez, Kimberly; Khanna, Rajesh

doi:10.1097/j.pain.0000000000002652

Cited by 2 publications

(1 citation statement)

References 16 publications

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“…In this study, we aimed to provide a comprehension analysis of TN-associated CACNA1H variants with regard to their impact on the functioning of Ca v 3.2 channels. Of the 19 variants reported [ 25 ], four had already been assessed for their impact on the biophysical properties of Ca v 3.2 channels and revealed a variant-dependent effect such that G563R and P566T produced a GoF of the channel, E286K caused a mild loss-of-function (LoF), and H526Y did not cause any alteration [ 17 , 30 ]. We now report the functional characterization of 13 additional variants.…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological and computational analysis of Cav3.2 channel variants associated with familial trigeminal neuralgia

et al. 2022

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Trigeminal neuralgia (TN) is a rare form of chronic neuropathic pain characterized by spontaneous or elicited paroxysms of electric shock-like or stabbing pain in a region of the face. While most cases occur in a sporadic manner and are accompanied by intracranial vascular compression of the trigeminal nerve root, alteration of ion channels has emerged as a potential exacerbating factor. Recently, whole exome sequencing analysis of familial TN patients identified 19 rare variants in the gene CACNA1H encoding for Cav3.2T-type calcium channels. An initial analysis of 4 of these variants pointed to a pathogenic role. In this study, we assessed the electrophysiological properties of 13 additional TN-associated Cav3.2 variants expressed in tsA-201 cells. Our data indicate that 6 out of the 13 variants analyzed display alteration of their gating properties as evidenced by a hyperpolarizing shift of their voltage dependence of activation and/or inactivation resulting in an enhanced window current supported by Cav3.2 channels. An additional variant enhanced the recovery from inactivation. Simulation of neuronal electrical membrane potential using a computational model of reticular thalamic neuron suggests that TN-associated Cav3.2 variants could enhance neuronal excitability. Altogether, the present study adds to the notion that ion channel polymorphisms could contribute to the etiology of some cases of TN and further support a role for Cav3.2 channels.

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Section: Introductionmentioning

confidence: 99%

Electrophysiological and computational analysis of Cav3.2 channel variants associated with familial trigeminal neuralgia

et al. 2022

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Central and peripheral contributions of T-type calcium channels in pain

Harding

Zamponi

2022

Mol Brain

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Chronic pain is a severely debilitating condition that reflects a long-term sensitization of signal transduction in the afferent pain pathway. Among the key players in this pathway are T-type calcium channels, in particular the Cav3.2 isoform. Because of their biophysical characteristics, these channels are ideally suited towards regulating neuronal excitability. Recent evidence suggests that T-type channels contribute to excitability of neurons all along the ascending and descending pain pathways, within primary afferent neurons, spinal dorsal horn neurons, and within pain-processing neurons in the midbrain and cortex. Here we review the contribution of T-type channels to neuronal excitability and function in each of these neuronal populations and how they are dysregulated in chronic pain conditions. Finally, we discuss their molecular pharmacology and the potential role of these channels as therapeutic targets for chronic pain.

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CaV3.2 calcium channels: new players in facial pain

Cited by 2 publications

References 16 publications

Electrophysiological and computational analysis of Cav3.2 channel variants associated with familial trigeminal neuralgia

Electrophysiological and computational analysis of Cav3.2 channel variants associated with familial trigeminal neuralgia

Central and peripheral contributions of T-type calcium channels in pain

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