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Assessment of temperature sensitivity of the TRPM2 channel

Bartok, Adam and Csanády, László (2021) Assessment of temperature sensitivity of the TRPM2 channel. In: 13th EBSA congress, July 24–28, 2021, Vienna, Austria.

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Abstract

TRPM2 belongs to the TRP family, and is expressed in neurons of the central nervous system, bone marrow, phagocytes, β-cells, and cardiomyocytes. It forms Ca2+-permeable nonselective cation channels that open under oxidative stress by simultaneous binding of intracellular Ca2+, ADP-ribose (ADPR), and PiP2 in the membrane. Malfunction of the channel has been linked to neurological disorders (AD, PD, ALS) as well as to pathological conditions that lead to apoptosis (cerebral stroke, myocardial infarction). Temperaturedependent activation of TRPM2 in warm-sensitive neurons underlies body heat control and the generation of fever. The channel may be a target to treat fever, chronic inflammations, diabetes or congenital hyperinsulinism. The biophysical background of temperature sensitivity of TRPM2 is yet unknown, and might reflect either temperature dependence of the intracellular concentrations of any of its three activating ligands, or intrinsic heat sensitivity of the TRPM2 itself. Therefore, we determined temperature dependence of TRPM2 gating parameters and apparent ligand binding affinities for Ca2+, ADPR, and PIP2 in inside-out patches from HEK-293 cells expressing human TRPM2, under temperature-controlled perfusion of the cytosolic surface. Our results unequivocally clarify and describe themechanism of temperature sensitivity of the TRPM2 channel.

Item Type: Conference or Workshop Item (Lecture)
Subjects: R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában > R850-854 Experimental medicine / kisérleti orvostudomány
Depositing User: Dr. Ádám Bartók
Date Deposited: 28 Sep 2021 12:31
Last Modified: 28 Sep 2021 12:31
URI: http://real.mtak.hu/id/eprint/131073

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