Blood flow into the cerebral microvasculature is regulated by TRPC3-dependent constriction of transitional pericytes.

Structural snapshots capture an ataxia-linked overactive ion channel in its open state and reveal a druggable site for inhibition.

Structural snapshots capture an ataxia-linked overactive ion channel in its open state and reveal a druggable site for inhibition.

Pericytes play a crucial role in regulating cerebral blood flow (CBF) through processes like vasomotion and neurovascular coupling (NVC). Recent work has identified different pericyte types at distinc...

Intensive and detailed investigations of the molecular function and cellular role of mammalian transient receptor potential canonical (TRPC) channels started back in the early 90th of the past cent...

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Structural snapshots capture an ataxia-linked overactive ion channel in its open state and reveal a druggable site for inhibition.

How localized Ca2+ signals orchestrate neural repair remains unclear. Here, we show that TRPC3-driven calcium microdomains direct nerve repair by coupling spatially confined Ca2+ signals to axon rege...

Blood flow into the cerebral microvasculature is regulated by TRPC3-dependent constriction of transitional pericytes.

A research group led by Assistant Professor Megumi Aimoto and Professor Akira Takahara at the Faculty of Pharmaceutical Sciences, Toho University, revealed that pyrazole-3 (Pyr3), a selective inhibitor of the transient receptor potential canonical-3 (TRPC3) channel, a calcium-permeable channel in the heart, prevents the persistence of atrial fibrillation. Atrial fibrillation is a tachyarrhythmia that occurs in the atria and is a major cause of stroke and heart failure. This study demonstrated that the TRPC3 channel is a promising new therapeutic target for atrial fibrillation.

Molecular Psychiatry - Pyrazole-derived TRPC3 antagonist ameliorates synaptic dysfunctions and memory deficits in Alzheimer’s disease models

A research group led by Assistant Professor Megumi Aimoto and Professor Akira Takahara at the Faculty of Pharmaceutical Sciences, Toho University, revealed that pyrazole-3 (Pyr3), a selective inhibitor of the transient receptor potential canonical-3 (TRPC3) channel, a calcium-permeable channel in the heart, prevents the persistence of atrial fibrillation. Atrial fibrillation is a tachyarrhythmia that occurs in the atria and is a major cause of stroke and heart failure. This study demonstrated that the TRPC3 channel is a promising new therapeutic target for atrial fibrillation.

All animal procedures were performed in accordance with the Animal Scientific Procedures Act and with the approval of the Institutional Animal Care and Use Committee (IACUC) at the University of Tennessee Health Science Center. The 5xFAD breeder mice were originally purchased from JAX (Stock #034840) and were bred via mating hemizygous transgenic males with wild-type B6SJLF1 breeders (Jackson Labs, Stock #100012), with the mutant retinal degeneration allele (Pde6b + /rd) bred out of the colony. TRPC3 heterozygous mice (+/-) were obtained from (JAX (Stock #016188) and mice were bred between heterozygous to obtain all three genotypes for analysis of P0-1 neurons from the littermates. APPKI mice (APPNL-G-F) were obtained from Dr. Takaomi C. Saito (RIKEN Brain Science Institute, Wakoshi, Saitama, Japan) and maintained via breeding between heterozygous mice. Human brain specimens for immunohistochemistry We used a convenience sample of specimens provided by the University of Kentucky AD Research Center (UK-ADRC) community-based autopsy cohort, and the work performed was approved by the University of Kentucky Institutional Review Board. All samples were obtained from individuals with informed consents at UK-ADRC. Aspects of the UK-ADRC autopsy cohort and biobank, from recruiting to neuropathological workups, have been described previously in detail [36, 37]. From...