TRPM4 Contributes to Subthreshold Membrane Potential Oscillations in Multiple Mouse Pacemaker Neurons

Li, Keyong; Shi, Yingtang; Gonye, Elizabeth C.; Bayliss, Douglas A.

doi:10.1523/eneuro.0212-21.2021

Cited by 10 publications

(7 citation statements)

References 41 publications

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“…Several studies suggested the role of TRPM4 in neuronal function on different brain regions including the hippocampus[21][31][32] the prefrontal cortex[33] and the pre-Bötzinger[34] complex however, most of these publications used pharmacological tools with questionable selectivity[25] to investigate TRPM4 function. Recently, two studies proved the expression of Trpm4 in brainstem pacemaker neurons using the ultrasensitive RNAscope in situ hybridization technique[35][36]. Our findings extend these results.…”

Section: Discussionsupporting

confidence: 86%

Transient receptor potential melastatin 4 (TRPM4) regulates hilar mossy cell loss in temporal lobe epilepsy

Mundrucz¹,

Kecskés²,

Henn-Mike³

et al. 2022

Preprint

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Mossy cells comprise a large fraction of excitatory neurons in the hippocampal dentate gyrus and their loss is one of the major hallmarks of temporal lobe epilepsy (TLE). The vulnerability of mossy cells in TLE is well known in animal models as well as in patients, however the mechanisms leading to cellular death is unclear. One possible explanation for their sensitivity is linked to their specific ion channel composition. TRPM4 is a Ca2+-activated non-selective cation channel regulating diverse physiological function of excitable cells. Here, we identified that TRPM4 is present and functionally active in hilar mossy cells. Furthermore, we showed that TRPM4 contributes to mossy cells death following status epilepticus and therefore modulates seizure susceptibility and epilepsy-related memory deficits in the chronic phase of TLE.

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Section: Discussionsupporting

confidence: 86%

Transient receptor potential melastatin 4 (TRPM4) regulates hilar mossy cell loss in temporal lobe epilepsy

Mundrucz¹,

Kecskés²,

Henn-Mike³

et al. 2022

Preprint

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“…4b ). Further, a TRPM4 blocker, CBA, that has no significant activity against TRPM8 49 , 50 , did not affect the lightening induced by cooling at any of the tested concentrations (Fig. 4c ).…”

Section: Resultsmentioning

confidence: 90%

TRPM8 thermosensation in poikilotherms mediates both skin colour and locomotor performance responses to cold temperature

2023

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Thermoregulation is a homeostatic process to maintain an organism’s internal temperature within a physiological range compatible with life. In poikilotherms, body temperature fluctuates with that of the environment, with both physiological and behavioral responses employed to modify body temperature. Changing skin colour/reflectance and locomotor activity are both well-recognized temperature regulatory mechanisms, but little is known of the participating thermosensor/s. We find that Xenopus laevis tadpoles put in the cold exhibit a temperature-dependent, systemic, and rapid melanosome aggregation in melanophores, which lightens the skin. Cooling also induces a reduction in the locomotor performance. To identify the cold-sensor, we focus on transient receptor potential (trp) channel genes from a Trpm family. mRNAs for several Trpms are present in Xenopus tails, and Trpm8 protein is present in skin melanophores. Temperature-induced melanosome aggregation is mimicked by the Trpm8 agonist menthol (WS12) and blocked by a Trpm8 antagonist. The degree of skin lightening induced by cooling is correlated with locomotor performance, and both responses are rapidly regulated in a dose-dependent and correlated manner by the WS12 Trpm8 agonist. We propose that TRPM8 serves as a cool thermosensor in poikilotherms that helps coordinate skin lightening and behavioural locomotor performance as adaptive thermoregulatory responses to cold.

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“…Several studies suggested the role of TRPM4 in neuronal function on different brain regions including the hippocampus [ 19 , 30 , 31 ], the prefrontal cortex [ 32 ], and the pre-Bötzinger [ 33 ] complex; however, most of these publications used pharmacological tools with questionable selectivity [ 24 ] to investigate TRPM4 function. Recently, two studies proved the expression of Trpm4 in brainstem pacemaker neurons using the ultrasensitive RNAscope in situ hybridization technique [ 34 , 35 ]. Our findings extend these results.…”

Section: Discussionmentioning

confidence: 99%

TRPM4 regulates hilar mossy cell loss in temporal lobe epilepsy

et al. 2023

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Background Mossy cells comprise a large fraction of excitatory neurons in the hippocampal dentate gyrus, and their loss is one of the major hallmarks of temporal lobe epilepsy (TLE). The vulnerability of mossy cells in TLE is well known in animal models as well as in patients; however, the mechanisms leading to cellular death is unclear. Results Transient receptor potential melastatin 4 (TRPM4) is a Ca2+-activated non-selective cation channel regulating diverse physiological functions of excitable cells. Here, we identified that TRPM4 is present in hilar mossy cells and regulates their intrinsic electrophysiological properties including spontaneous activity and action potential dynamics. Furthermore, we showed that TRPM4 contributes to mossy cells death following status epilepticus and therefore modulates seizure susceptibility and epilepsy-related memory deficits. Conclusions Our results provide evidence for the role of TRPM4 in MC excitability both in physiological and pathological conditions.

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TRPM4 Contributes to Subthreshold Membrane Potential Oscillations in Multiple Mouse Pacemaker Neurons

Cited by 10 publications

References 41 publications

Transient receptor potential melastatin 4 (TRPM4) regulates hilar mossy cell loss in temporal lobe epilepsy

Transient receptor potential melastatin 4 (TRPM4) regulates hilar mossy cell loss in temporal lobe epilepsy

TRPM8 thermosensation in poikilotherms mediates both skin colour and locomotor performance responses to cold temperature

TRPM4 regulates hilar mossy cell loss in temporal lobe epilepsy

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