A subsequent group noticed that this mutation is in a region important for modulation by G protein-coupled receptors (GPCRs). GPCR activation leads to inhibition of wild-type CaV2.1 currents. R192Q mutant channel currents are also decreased by GPCR activation, but by a smaller amount. A more recent group has confirmed some of these results by creating a R192Q knock-in mouse. They confirmed that the R192Q mutant activates at more negative potentials and that neurons producing these channels have much larger whole-cell current. This resulted in a much larger quantal content (the number of neurotransmitter packets released per action potential) and generally enhanced neurotransmitter release in R192Q-expressing neurons versus wild-type. Consequently, these mutant mice were more susceptible to cortical-spreading-depression than their wild-type counterparts. The most recent experiments on this mutant, however, have contradicted some of these results. In CaV2.1 knockout neurons transfected with human channels, P/Q-type currents from mutant channels are actually smaller than their wild-type counterpart. They also found a significant decrease in calcium influx during depolarization, leading to decreased quantal content, in mutant versus wild-type expressing neurons. Neurons expressing mutant channels were also less able to mediate inhibitory input and have smaller inhibitory postsynaptic currents through P/Q-type channels. Further testing with this and other mutants is required to determine their end effect on human physiology. FHM2 (ATP1A2)
The second subtype of familial hemiplegic migraine, FHM2, is caused by mutations in the gene ATP1A2 that encodes a Na+/K+-ATPase. This Na+/K+-ATPase is heavily expressed in astrocytes and helps to set and maintain their reversal potential.
Lipoatrophic diabetes is a type of diabetes mellitus presenting with severe lipodystrophy in addition to the traditional signs of diabetes. See also
Familial partial lipodystrophy
Congenital generalized lipodystrophy

External links

Iglesias P, Alvarez Fidalgo P, Codoceo R, Díez J (2004). "Lipoatrophic diabetes in an elderly woman: clinical course and serum adipocytokine concentrations". Endocr J. 51 (3): 279–86. doi:10.1507/endocrj.51.279. PMID 15256772. Morse A, Whitaker M (2000). "Successful pregnancy in a woman with lipoatrophic diabetes mellitus. A case report". J Reprod Med. 45 (10): 850–2. PMID 11077638. Meyer L, Hadjadj S, Guerci B, Delbachian I, Ziegler O, Drouin P (1998). "Lipoatrophic diabetes mellitus treated by continuous subcutaneous insulin infusion". Diabetes Metab. 24 (6): 544–6. PMID 9932222.