Presentation Title (IN ALL CAPS)

METFORMIN MODULATES ACID-SENSING ION CHANNEL 3

Departmental Affiliation and City, State, Zip for All Authors

Carter Butson UNT Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, Texas 76107; Theodore Price The University of Texas at Dallas 800 W. Campbell Rd., BSB 14 Richardson, TX 75080; Gregory Dussor The University of Texas at Dallas 800 W. Campbell Rd., BSB 14 Richardson, TX 75080; Eric B Gonzales UNT Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, Texas 76107

Scientific Abstract

Acid-sensing ion channels (ASIC) are proton-gated cation channels located throughout the nervous system. ASICs detect pH fluctuations especially in epilepsy and stroke. Guanidine compounds have been found to have a modulatory effect on these channels. There are only a handful of ligands that affect ASICs, even fewer are selective. We studied the guanidine compound and diabetes medication, metformin, on an isolated ASIC subtype, ASIC3. Our data indicates that metformin is an antagonist of ASIC3 in the millimolar range, indicating metformin is a low affinity antagonist. Metformin at 1 mM did not show an effect on ASIC3 pH sensitivity. Based on our data, metformin shares properties of other guanidine compounds in having efficacy on ASIC3. We speculate that metformin differs from other ASIC3 guanidine ligands due to metformin’s smaller molecular volume and the presence of two guanidine moieties. Future experiments will elucidate the molecular properties of guanidine compounds that influence efficacy and potency on ASIC3.

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METFORMIN MODULATES ACID-SENSING ION CHANNEL 3

Acid-sensing ion channels (ASIC) are proton-gated cation channels located throughout the nervous system. ASICs detect pH fluctuations especially in epilepsy and stroke. Guanidine compounds have been found to have a modulatory effect on these channels. There are only a handful of ligands that affect ASICs, even fewer are selective. We studied the guanidine compound and diabetes medication, metformin, on an isolated ASIC subtype, ASIC3. Our data indicates that metformin is an antagonist of ASIC3 in the millimolar range, indicating metformin is a low affinity antagonist. Metformin at 1 mM did not show an effect on ASIC3 pH sensitivity. Based on our data, metformin shares properties of other guanidine compounds in having efficacy on ASIC3. We speculate that metformin differs from other ASIC3 guanidine ligands due to metformin’s smaller molecular volume and the presence of two guanidine moieties. Future experiments will elucidate the molecular properties of guanidine compounds that influence efficacy and potency on ASIC3.

Manuscript Number

1001