1.A.9.5.5
Human GABA-A (hGABA-A) rho1 receptor of 479 aas and 4 TMSs. The guanidine compound, amiloride, antagonized the heteromeric GABA-A, glycine, and nicotinic acetylcholine receptors, but it exhibits characteristics consistent with a positive allosteric modulator for the hGABA-A rho1 receptor (Snell and Gonzales 2016).  Picrotoxinin binds to both GABAA-rho1 and -rho2 in the homomeric channels, but to GABAA-rho2 with 10x higher affinity (Naffaa and Samad 2016). The inhibitory site for ethanol in GABAA rho1 receptors regulates acute functional tolerance to moderate ethanol intoxication. Low sensitivity to alcohol intoxication is linked to risk for the development of alcohol dependence in humans (Blednov et al. 2017). Positive and negative allosteric modulators of GABAA receptors have been reviewed (Olsen 2018). A single amino acid change within the ion-channel domain accelerates desensitization and increases taurine agonism (Martínez-Torres and Miledi 2013).