HOMOMERIC BETA-1 GAMMA-AMINOBUTYRIC ACID(A) RECEPTOR-ION CHANNELS - EVALUATION OF PHARMACOLOGICAL AND PHYSIOLOGICAL-PROPERTIES

The ubiquitous distribution of gamma-aminobutyric acid(A) (GABA(A)) re ceptor beta subunits throughout the central nervous system is in accor d with a vital role in receptor structure and function. Homomeric beta subunits have been reported to be either GABA-gated or capable of for ming anion-selective channels that lacked GABA-gating properties. With electrophysiological recording techniques, we examined the properties of the murine beta 1 subunit, addressed whether the homomeric recepto r is expressed independently from the host cell's genome, and investig ated whether these channels can open spontaneously, Murine beta 1 subu nits, expressed in Xenopus oocytes or A293 cells, were unaffected by G ABA or bicuculline; however, the resting membrane conductances were re duced by picrotoxin, zinc, or penicillin-G. In comparison, the express ion of bovine beta 1 subunits formed GABA-gated Cl- channels. For muri ne beta 1 subunits, both pentobarbitone and propofol increased the mem brane conductance, although the benzodiazepine ligands flurazepam, flu mazenil, and 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate were i nactive. Oocytes injected with murine beta 1 cRNA in the presence of a ctinomycin D (to block host cell DNA transcription) expressed beta 1 c hannels that were indistinguishable from those derived from previous c DNA injections in cells capable of normal transcription. Single-channe l recording from murine beta 1 cDNA-injected oocytes revealed spontane ously opening channels with a main state conductance of 18 pS. Picroto xin inhibited the channel openings by reducing the probability of open ing. We concluded that murine beta 1 subunits can form functional ion channels that are not gated by GABA but can be closed by some noncompe titive GABA antagonists. Interestingly, previous observations of spont aneously opening ion channels with properties similar to those found f or the murine beta 1 receptor suggest that a limited expression of hom omeric beta subunit-ion channels may exist in vivo.