Multiple GABA receptors via modulated gene expression

Joshua W. Fost jwfost at rodin.Princeton.EDU
Wed Oct 14 10:58:58 EST 1992


I recently had a discussion about GABA receptors, and there was some
interesting speculation about how the modulated gene expression for
different subtypes of GABAA, especially, could lead to very funky
kinds of plasticity. GABAA is a tetramer, with subunits alpha, beta,
gamma, delta. However, you can make a functional GABA-agonist gated
Cl- channel by using almost any combination of these subunits. E.g.,
two alpha subunits and two betas will work. However, many different
versions of each subtype have been discovered. There are 6 alphas so
far, 3 gammas, etc. I'm not sure that it has been demonstrated that
the whole diversity can exist in one animal, but certainly there is
some. If you in-situ hybridize for antisense mRNA of different alpha 
subunits, you see that the different subunits *do not have the same 
distribution.* This is especially interesting since the particular
combination you use will confer different functional properties to
the receptor complex. For example, sensitivity to benzodiazepines is
largely a function of the alpha subunit. So, the idea is, some 2nd 
messenger could modulate the gene expression for the subunits, and
a given cell could end up (if it had all the so-far-discovered versions
of the subunits, which it probably doesn't, but what the heck, let's
handwave) with up to 31,000 different GABA receptors. Wow! So: does
anyone know if this kind of plasticity has actually been observed, if
more direct data exists, and/or whether such possibilities exist for
other NTs?

By the way, most of my references are from TIPS articles, and a great
book by Barnard & Costa, "Allosteric modulation of amino acid
receptors." Or something like that. 



More information about the Neur-sci mailing list