biostudies-literatureDemaree ISNIA NIH HHSNHLBI NIH HHSNINDS NIH HHSNIAMS NIH HHSNIGMS NIH HHSNIH HHS2019https://www.ebi.ac.uk/biostudies/studies/S-EPMC11640535biostudies-literatureUnknown13(23)<h4>Background</h4>TRPC5 proteins form plasma membrane cation channels and are expressed in the nervous and cardiovascular systems. TRPC5 activation leads to cell depolarization and increases neuronal excitability, whereas a homologous TRPC1 inhibits TRPC5 function via heteromerization. The mechanism underlying the inhibitory effect of TRPC1 in TRPC5/TRPC1 heteromers remains unknown.<h4>Methods</h4>We used electrophysiological techniques to examine the roles of subunit stoichiometry and positively charged luminal residues of TRPC1 on TRPC5/TRPC1 function. We also performed molecular dynamics simulations.<h4>Results</h4>We found that increasing the relative amount of TRPC1 in TRPC5/TRPC1 heteromers reduced histamine-induced cation influx through the heteromeric channels. Consistently, histaCellsEffects of TRPC1's Lysines on Heteromeric TRPC5-TRPC1 Channel Function.PMC11640535R01 AG075132R01 GM111639HL083381, HL115140, NS102415, AG075132R01 HL115140R01 GM115844R01 AR083130R01 NS102415R01 HL083381Hoang QQDemaree ISObukhov AGTennessen KWhite FAKumar SfalseEffects of TRPC1's Lysines on Heteromeric TRPC5-TRPC1 Channel Function.<h4>Background</h4>TRPC5 proteins form plasma membrane cation channels and are expressed in the nervous and cardiovascular systems. TRPC5 activation leads to cell depolarization and increases neuronal excitability, whereas a homologous TRPC1 inhibits TRPC5 function via heteromerization. The mechanism underlying the inhibitory effect of TRPC1 in TRPC5/TRPC1 heteromers remains unknown.<h4>Methods</h4>We used electrophysiological techniques to examine the roles of subunit stoichiometry and positively charged luminal residues of TRPC1 on TRPC5/TRPC1 function. We also performed molecular dynamics simulations.<h4>Results</h4>We found that increasing the relative amount of TRPC1 in TRPC5/TRPC1 heteromers reduced histamine-induced cation influx through the heteromeric channels. Consistently, hista2024-01-01T00:00:00Z2024 Dec2026-04-23T03:25:49.53Z2025-04-04T01:54:20.975ZS-EPMC116405353968276710.3390/cells13232019