Normal or abnormal? - Heat sensing mechanism of the type 1 ryanodine receptor studied by microscopic heating and temperature imaging

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  • 正常？異常？ー局所加熱と温度イメージングで探るリアノジン受容体の熱知覚の仕組み

Abstract

<p>Protein activity is temperature sensitive. The temperature sensitivity is usually examined by adjusting the room or medium temperature. However, as these global heating and cooling processes are slow, biological samples can be thermally damaged at higher temperatures. This issue can be avoided by limiting volume of the heat source, so that the temperature gradient created around the small heat source is immediately dissipated by heat diffusion to the surrounding media when the power supply is terminated. We have applied an optically controlled rapid heating method based on focused infrared laser irradiation to examine the thermal sensitivity of the type 1 ryanodine receptor. Here, I will briefly introduce our results that mutants of RyR1 implicated in malignant hyperthermia are more heat-sensitive than the wild type. Detailed analysis led to the discovery of the heat-induced Ca2+ release (HICR) mechanism in RyR1 channels. HICR is proposed to form a positive feedback loop between thermogenesis during malignant hyperthermia and the heat-induced Ca2+ release through RyR1 mutants. More recently, we have extended the variation of RyR1 mutants examined, which are providing us with insights into the molecular mechanism of the heat-hypersensitivity.</p>

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