Mutation of α1GT-type Calcium Channels in Mice Does Not Change Anesthetic Requirements for Loss of the Righting Reflex and Minimum Alveolar Concentration but Delays the Onset of Anesthetic Induction

Petrenko, Andrey B.; Teräs, Mika; Kohno, Tatsuro; Sakimura, Kenji; Baba, Hiroshi

doi:10.1097/01.anes.0000267601.09764.e6

Cited by 50 publications

(44 citation statements)

References 25 publications

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“…or ethanol (3.5 g/kg) administration (Table 1). Though findings appeared to be in conflict with previous results showing no significant changes of LORR following the use of several general anesthetics (32), this discrepancy is most probably due to the difference of exposure or anesthetics dosages used to induce LORR. Although the 50% effective concentration for LORR in Ca V 3.1 KO mice was not altered, the latencies to develop LORR of Ca V 3.1 KO mice after exposure to anesthetics, such as isoflurane, halothane, sevoflurane, and pentobarbital, were longer (32), which our results have confirmed.…”

Section: Discussioncontrasting

confidence: 97%

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Altered thalamocortical rhythmicity and connectivity in mice lacking Ca _V 3.1 T-type Ca ²⁺ channels in unconsciousness

Choi

Lee

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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In unconscious status (e.g., deep sleep and anesthetic unconsciousness) where cognitive functions are not generated there is still a significant level of brain activity present. Indeed, the electrophysiology of the unconscious brain is characterized by well-defined thalamocortical rhythmicity. Here we address the ionic basis for such thalamocortical rhythms during unconsciousness. In particular, we address the role of Ca V 3.1 T-type Ca 2+ channels, which are richly expressed in thalamic neurons. Toward this aim, we examined the electrophysiological and behavioral phenotypes of mice lacking Ca V 3.1 channels (Ca V 3.1 knockout) during unconsciousness induced by ketamine or ethanol administration. Our findings indicate that Ca V 3.1 KO mice displayed attenuated low-frequency oscillations in thalamocortical loops, especially in the 1-to 4-Hz delta band, compared with control mice (Ca V 3.1 WT). Intriguingly, we also found that Ca V 3.1 KO mice exhibited augmented highfrequency oscillations during unconsciousness. In a behavioral measure of unconsciousness dynamics, Ca V 3.1 KO mice took longer to fall into the unconscious state than controls. In addition, such unconscious events had a shorter duration than those of control mice. The thalamocortical interaction level between mediodorsal thalamus and frontal cortex in Ca V 3.1 KO mice was significantly lower, especially for delta band oscillations, compared with that of Ca V 3.1 WT mice, during unconsciousness. These results suggest that the Ca V 3.1 channel is required for the generation of a given set of thalamocortical rhythms during unconsciousness. Further, that thalamocortical resonant neuronal activity supported by this channel is important for the control of vigilance states.electroencephalogram | local field potential | mediodorsal thalamus | coherence T halamocortical interactive rhythmic activities are well-defined physiological correlates of both conscious and unconscious conditions (1, 2). From a functional perspective, abnormal slow cortical rhythms and their synchronized network dynamics are omnipresent correlates of unconscious states, such as coma and general anesthesia (3, 4). Moreover, a dynamic alteration of coherence as well as coupling/uncoupling in thalamocortical circuits also can be characterized as likely correlates of unconsciousness (3-5).Since the discovery of low threshold, T-type Ca 2+ channels (6, 7) and the subsequent studies of intrinsic electrophysiological properties in the thalamic neurons (8, 9), T-type Ca 2+ channels have been implicated in many physiological and pathological brain states (for a review, see ref. 10). The ionic conductances they support have been shown to generate synchronized oscillatory activity in thalamocortical circuits through calcium-dependent low-threshold spikes (LTSs). Indeed, these LTSs, generated by "deinactivation" of T-type Ca 2+ channels, underlie thalamic burst firing. This activity is reflected as high-amplitude low-frequency oscillations in electroencephalography, and its presence is recognized...

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Section: Discussioncontrasting

confidence: 97%

“…Ca V 3.1 null KO mice and their littermate controls (WT) were generated by mating heterozygotes of Ca V 3.1 (C57BL/6) from RIKEN BioResource Center (32). Mice were housed with free access to food and water under controlled temperature conditions.…”

Section: Methodsmentioning

confidence: 99%

Altered thalamocortical rhythmicity and connectivity in mice lacking Ca _V 3.1 T-type Ca ²⁺ channels in unconsciousness

Choi

Lee

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Deletion of the Ca V 3.1 gene did not result in detectable morphological abnormalities (27,28). KO mice did not display abnormal behavior in confined laboratory conditions: a 55-h activity survey did not indicate alteration of the global circadian activity (Fig.…”

Section: T-type Channel Blockade Prevents Ltp Induction With No Effecmentioning

confidence: 93%

“…Mice lacking the cacna1g gene (encoding Ca V 3.1) were produced as previously described (28). (21) was made up as a 10 mM stock solution in dimethyl sulfoxide (DMSO); aliquots were kept at -20°C and diluted for use as indicated at 1 μM concentrations known to block T-type calcium channels (21,23).…”

Section: Methodsmentioning

confidence: 99%

T-type channel blockade impairs long-term potentiation at the parallel fiber–Purkinje cell synapse and cerebellar learning

Bouvier

Schonewille

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Ca V 3.1 T-type channels are abundant at the cerebellar synapse between parallel fibers and Purkinje cells where they contribute to synaptic depolarization. So far, no specific physiological function has been attributed to these channels neither as charge carriers nor more specifically as Ca 2+ carriers. Here we analyze their incidence on synaptic plasticity, motor behavior, and cerebellar motor learning, comparing WT animals and mice where T-type channel function has been abolished either by gene deletion or by acute pharmacological blockade. At the cellular level, we show that Ca V 3.1 channels are required for long-term potentiation at parallel fiber-Purkinje cell synapses. Moreover, basal simple spike discharge of the Purkinje cell in KO mice is modified. Acute or chronic T-type current blockade results in impaired motor performance in particular when a good body balance is required. Because motor behavior integrates reflexes and past memories of learned behavior, this suggests impaired learning. Indeed, subjecting the KO mice to a vestibulo-ocular reflex phase reversal test reveals impaired cerebellum-dependent motor learning. These data identify a role of low-voltage activated calcium channels in synaptic plasticity and establish a role for Ca V 3.1 channels in cerebellar learning.

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“…Modulation of GABA A receptors in this manner is known to be an important part of the mechanism of action for many anesthetics. More recent studies, however, have shown that general anesthetics can influence a number of voltage and ligand-gated ion channels (Campagna et al 2003;Chen et al 2007;Hemmings et al 2005;Krasowski and Harrison 1999;Petrenko et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Isoflurane Inhibits the Neurotransmitter Release Machinery

Herring¹,

Xie²,

Marks³

et al. 2009

Journal of Neurophysiology

109

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Mutation of α1GT-type Calcium Channels in Mice Does Not Change Anesthetic Requirements for Loss of the Righting Reflex and Minimum Alveolar Concentration but Delays the Onset of Anesthetic Induction

Cited by 50 publications

References 25 publications

Altered thalamocortical rhythmicity and connectivity in mice lacking Ca _V 3.1 T-type Ca ²⁺ channels in unconsciousness

Altered thalamocortical rhythmicity and connectivity in mice lacking Ca _V 3.1 T-type Ca ²⁺ channels in unconsciousness

T-type channel blockade impairs long-term potentiation at the parallel fiber–Purkinje cell synapse and cerebellar learning

Isoflurane Inhibits the Neurotransmitter Release Machinery

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Mutation of α1GT-type Calcium Channels in Mice Does Not Change Anesthetic Requirements for Loss of the Righting Reflex and Minimum Alveolar Concentration but Delays the Onset of Anesthetic Induction

Cited by 50 publications

References 25 publications

Altered thalamocortical rhythmicity and connectivity in mice lacking Ca V 3.1 T-type Ca 2+ channels in unconsciousness

Altered thalamocortical rhythmicity and connectivity in mice lacking Ca V 3.1 T-type Ca 2+ channels in unconsciousness

T-type channel blockade impairs long-term potentiation at the parallel fiber–Purkinje cell synapse and cerebellar learning

Isoflurane Inhibits the Neurotransmitter Release Machinery

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Product

Resources

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Altered thalamocortical rhythmicity and connectivity in mice lacking Ca _V 3.1 T-type Ca ²⁺ channels in unconsciousness

Altered thalamocortical rhythmicity and connectivity in mice lacking Ca _V 3.1 T-type Ca ²⁺ channels in unconsciousness