Method for controlling membrane potential-dependent ion channel through type i taste receptors (t1rs)

A method for controlling the activation current of voltage-gated ion channels in nerve cells or cardiomyocytes using a composition comprising a Type I taste receptor ligand that specifically binds to a Type I taste receptor and acts as an agonist or antagonist.

A method for measuring changes in the amplification or suppression effects of VGSC and/or VGKC activation currents mediated by human Type I taste receptors, and evaluating the improvement effects of diseases caused by such amplification or suppression effects induced by test substances, comprising:

• (i) human suspension cells endogenously expressing Type I taste receptors and VGSC and/or VGKC, and
• (ii) suspension cells derived from blood cells or animal cells forcibly expressing human-derived Type I taste receptor genes and human-derived VGSC and/or VGKC genes, wherein the Type I taste receptor has been replaced with a human-derived Type I taste receptor gene, selected from either of the suspension cells, and measured by the autopatch clamp membrane potential fixation method.

A method for measuring changes in the amplification effects of neuronal or cardiomyocyte hyperexcitation mediated by human Type I taste receptors, and evaluating the improvement effects of diseases caused by such hyperexcitation induced by test substances, comprising:

• (i) cultured human nerve cells, cultured human cardiomyocytes, or other human cultured cells expressing Type I taste receptors on their surface, and
• (ii) mouse or other cultured animal cells expressing Type I taste receptors, wherein the T1R1, T1R2, or T1R3 genes have been replaced with human-derived genes, selected from either of the cultured cells, and measured by the patch clamp method (current clamp mode), NanoTouch method, MEA method, or using fluorescent membrane potential-sensitive reagents or fluorescent intracellular calcium-sensitive reagents.

A method for measuring changes in the barrier function impairment of vascular cells mediated by Type I taste receptors in the human brain or blood vessels, and evaluating the improvement effects of diseases caused by such barrier function impairment induced by test substances, comprising:

• (i) cultured human vascular endothelial cells or other sheet-forming human cultured cells expressing Type I taste receptors on their surface, and
• (ii) mouse or other cultured animal cells expressing Type I taste receptors, wherein the T1R1, T1R2, or T1R3 genes have been replaced with human-derived genes, selected from either of the cultured cells, and measured by the change in impedance (resistance) values of the cells cultured in sheet form on a conductive plate.

A method for measuring changes in the barrier function impairment of vascular cells or the decrease in plasticity of nerve cells mediated by Type I taste receptors, and evaluating the improvement effects of diseases caused by such impairments induced by test substances, comprising:

• (i) cultured human vascular endothelial cells, cultured human nerve cells, or other cultured human cells expressing Type I taste receptors on their surface, and
• (ii) mouse or other cultured animal cells expressing Type I taste receptors, wherein the T1R1, T1R2, or T1R3 genes have been replaced with human-derived genes, selected from either of the cultured cells, and measured by observing and measuring changes in cell morphology and dynamics, and/or changes in area or volume, and/or changes in the contraction and motility of neurites.