| First Author | Lor C | Year | 2020 |
| Journal | Int J Mol Sci | Volume | 21 |
| Issue | 24 | PubMed ID | 33333797 |
| Mgi Jnum | J:340436 | Mgi Id | MGI:7529328 |
| Doi | 10.3390/ijms21249534 | Citation | Lor C, et al. (2020) Isoflurane Potentiation of GABA(A) Receptors Is Reduced but Not Eliminated by the beta3(N265M) Mutation. Int J Mol Sci 21(24) |
| abstractText | Background: Mice carrying the GABA(A) receptor beta3(N265M) point mutation, which renders receptors incorporating beta3-subunits insensitive to many general anesthetics, have been used experimentally to link modulation of different receptor subtypes to distinct behavioral endpoints. Remarkably, however, the effect of the mutation on the susceptibility to modulation by isoflurane (a standard reference agent for inhalational vapors) has never been tested directly. Therefore, we compared the modulation by isoflurane of expressed alpha5beta3(N265M)gamma2L receptors with their wild type counterparts. Methods: Using whole-cell electrophysiological recording and rapid solution exchange techniques, we tested the effects of isoflurane at concentrations ranging from 80 muM to 320 muM on currents activated by 1 muM GABA. We measured drug modulation of wild-type alpha5beta3gamma2L GABA(A) receptors and their counterparts harboring the beta3(N265M) mutation. Results: Currents elicited by GABA were enhanced two- to four-fold by isoflurane, in a concentration-dependent manner. Under the same conditions, receptors incorporating the beta3(N265M) mutation were enhanced by approximately 1.5- to two-fold; i.e., modulation by isoflurane was attenuated by approximately one-half. Direct activation by isoflurane was also present in mutant receptors but also attenuated. Conclusions: In contrast to the complete insensitivity of beta3(N265M) mutant receptors to etomidate and propofol, the mutation has only a partial effect on receptor modulation by isoflurane. Therefore, the persistence of isoflurane effects in mutant mice does not exclude a possible contribution of beta3-GABA(A) receptors. |
