Down-regulation of T-type Cav3.2 channels by hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1): Evidence of a signaling complex

Fan, Jing; Gandini, María A.; Zhang, Fang-Xiong; Chen, Lina; Souza, Ivana A.; Zamponi, Gerald W.

doi:10.1080/19336950.2017.1326233

Cited by 13 publications

(10 citation statements)

References 26 publications

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“…Indeed, blocking or transgenic elimination of P/Q-type calcium channels have been described to prevent the generation of gamma band oscillations [30,37,38]. T-type and HCN channels are physically associated [39] to underlie low-frequency oscillatory activity at the thalamocortical level [33,38,39,40]. Indeed, T-type channels are key elements mediating the sensitivity to psychostimulants [19,28], consistent with the observed enhancement in low frequency oscillatory activity after METH [41,42] and changes in protein levels of T-type channels mediated by cocaine [43] administration.…”

Section: Discussionmentioning

confidence: 99%

Effects of methamphetamine on locomotor activity and thalamic gene expression in leptin-deficient obese mice

González¹,

González²,

Bisagno³

et al. 2017

Transl Brain Rhythmicity

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Leptin is an adipose-derived hormone that regulates energy balance. Leptin receptors are expressed in extrahypothalamic sites and several reports showed that leptin can influence feeding and locomotor behavior via direct actions on dopaminergic neurons. The leptin deficient mouse (ob/ob) has been used as an animal model of blunted leptin action, and presents with obesity and mild type 2 diabetes. We used ob/ob mice to study the effect of repeated 7-day methamphetamine (METH) administration analyzing locomotion, behavioral sensitization, and somatosensory thalamic mRNA expression of voltage-gated calcium channels and glutamatergic receptors using RT-PCR. We observed reduced METH-mediated responses in ob/ob mice associated with enhanced in mRNA expression of key voltage-gated and glutamate receptors in the somatosensory thalamus. Results described here are important for understanding the control of locomotion and thalamocortical excitability by leptin.

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Section: Discussionmentioning

confidence: 99%

Effects of methamphetamine on locomotor activity and thalamic gene expression in leptin-deficient obese mice

González¹,

González²,

Bisagno³

et al. 2017

Transl Brain Rhythmicity

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“…Our results are also consistent with previous reports, describing how intracellular Ca 2+ released from internal stores finally shaped LTS in reticular thalamic neurons (Coulon et al 2009). On the other hand, the observed increase of I H density after an acute "PACO"-like binge administration would stabilize the resting potential of VB neurons (Meuth et al 2006;Brennan et al 2016;Zobeiri et al 2019), enhancing even more the amplitude of LTS, given the functional and physical association between HCN and T-type channels (Fan et al 2017).…”

Section: Discussionmentioning

confidence: 97%

“…Our results suggested that the combined administration of cocaine and caffeine ("PACO"-like binge) prevented the increase of I T that was observed in separately administrations of cocaine or caffeine. HCN channels have been described to interact with T-type calcium channels (Fan et al 2017) and they are key channels modulating the resting membrane potential (RMP) in thalamocortical neurons (Meuth et al 2006;Budde et al 2008). Figure 2a shows that the RMP was depolarized by1 0 mV after PACO-like and cocaine binges (ANOVA, p < 0.05), according to the observed increase of I H current density.…”

Section: Characterization Of Both H-type and T-type Currents In Thalamentioning

confidence: 89%

“…T-type and HCN channels are physically and functionally associated (Huang et al 2011;Fan et al 2017) to underlie lowfrequency oscillatory activity at the thalamocortical level that can be characterized using electroencephalography (EEG) (Llinás et al 2007;Urbano et al 2009;Huang et al 2011). Indeed, T-type channels have been described as key elements involved in the sensitivity to psychostimulants (Bisagno et al 2010;Goitia et al 2013Goitia et al , 2016Gangarossa et al 2014).…”

Section: Controlmentioning

confidence: 99%

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Simultaneous administration of cocaine and caffeine dysregulates HCN and T-type channels

et al. 2020

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Rationale The abuse of psychostimulants has adverse consequences on the physiology of the central nervous system. In Argentina, and other South American countries, coca paste or "PACO" (cocaine and caffeine are its major components) is massively consumed with deleterious clinical consequences for the health and well-being of the general population. A scant number of studies have addressed the consequences of stimulant combination of cocaine and caffeine on the physiology of the somatosensory thalamocortical (ThCo) system. Objectives Our aim was to study ion conductances that have important implications regulating sleep-wake states 24-h after an acute or chronic binge-like administration of a cocaine and caffeine mixture following previously analyzed pasta base samples ("PACO"-like binge") using mice. Methods We randomly injected (i.p.) male C57BL/6JFcen mice with a binge-like psychostimulants regimen during either 1 day (acute) or 1 day on/1 day off during 13 days for a total of 7 binges (chronic). Single-cell patch-clamp recordings of VB neurons were performed in thalamocortical slices 24 h after the last psychostimulant injection. We also recorded EEG/EMG from mice 24 h after being systemically treated with chronic administration of cocaine + caffeine versus saline, vehicle. Results Our results showed notorious changes in the intrinsic properties of the VB nucleus neurons that persist after 24-h of either acute or chronic binge administrations of combined cocaine and caffeine ("PACO"-like binge). Functional dysregulation of HCN (hyperpolarization-activated cyclic nucleotide-gated) and T-type VGC (voltage-gated calcium) channels was described 24-h after acute/chronic "PACO"-like administrations. Furthermore, intracellular basal [Ca 2+ ] disturbances resulted a key factor that modulated the availability and the activation of T-type channels, altering T-type "window currents." As a result, all these changes ultimately shaped the low-threshold spikes (LTS)-associated Ca 2+ transients, regulated the membrane excitability, and altered sleep-wake transitions. Conclusion Our results suggest that deleterious consequences of stimulants cocaine and caffeine combination on the thalamocortical physiology as a whole might be related to potential neurotoxic effects of soaring intracellular [Ca 2+ ].

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“…For example, the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model has altered physiology when these channels contain exon 25, a splice variant transcript that is highly expressed in the thalamus [12]. Moreover, it is possible that mutations may compromise interactions with binding partners such as HCN channels [13] without affecting channel function per se. Altogether, there is considerable evidence linking Cav3.2 mutations to epilepsy in rodent models and humans.…”

Section: Introductionmentioning

confidence: 99%

Pathogenic Cav3.2 channel mutation in a child with primary generalized epilepsy

et al. 2019

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Two paternally-inherited missense variants in CACNA1H were identified and characterized in a 6-year-old child with generalized epilepsy. Febrile and unprovoked seizures were present in this child. Both variants were expressed in cis or isolation using human recombinant Cav3.2 calcium channels in tsA-201 cells. Whole-cell patch-clamp recordings indicated that one variant (c.3844C > T; p.R1282W) caused a significant increase in current density consistent with a pathogenic gain-of-function phenotype; while the other cis-related variant (c.5294C > T; p.A1765V) had a benign profile.

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Down-regulation of T-type Cav3.2 channels by hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1): Evidence of a signaling complex

Cited by 13 publications

References 26 publications

Effects of methamphetamine on locomotor activity and thalamic gene expression in leptin-deficient obese mice

Effects of methamphetamine on locomotor activity and thalamic gene expression in leptin-deficient obese mice

Simultaneous administration of cocaine and caffeine dysregulates HCN and T-type channels

Pathogenic Cav3.2 channel mutation in a child with primary generalized epilepsy

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