Human GABA_A g2 -- Arg 43

hArg43Gln

This mutation has been correlated with childhood absence epilepsy and febrile seizures.

The GABA EC₅₀ did not change with this mutation. Diazepam enhanced the a1b3g2L(R43Q) GABA_A receptor-mediated currents and this was similar to that observed for wild-type a1b3g2L.

The mean peak amplitude of a1b3g2(R43Q) was significantly smaller than either a1b3g2L or a1b3g2L(K289M). Deactivation was not affected by the g2L(R43Q) mutation.

The single channel conductance was unaltered, and the R43Q mutation did not change the pattern of burst-like openings.

Macdonald RL, Bianch MT, Feng H (2003) Mutations Linked to Generalized epilepsy in Humans Reduce GABA_A Receptor Current. Experimental Neurology 184: S58-S67

Bianchi MT, Luyan S, Zhang H, Macdonald RL (2002) Two Different Mechanisms of Disinhibition Produced by GABA_A Receptor Mutations Linked to Epilepsy in Humans The Journal of Neuroscience 22(12):5321-5327

In contrast to Bianchi et al., 2002, Bowser and colleagues (2002) found that receptors containing a1b2g2(R43Q) deactivated significantly more slowly than WT receptors. There was an increase in the rate of desensitization during long pulses of saturating GABA. The mutation caused a small reduction in the modulation of the GABA-activated by flunitrazepam.

Bowser DN, Wagner DA, Czajkowski C, Cromer BA, Parker MW, Wallace RH, Harkin LA, Mulley JC, Marini C, Berkovic SF, Williams DA, Jones MV, Petrou S (2002) Altered Kinetics and Benzodiazepine Sensitivity of a GABA_A Receptor Subunit Mutation [g2(R43Q)] Found in Human Epilepsy. Proceedings of the National Academy of Sciences 99(23):15170-15175

mArg42Gln

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