Reference

Depolarizing action of GABA (g-aminobutyric acid) on myelinated fibers of peripheral nerves

Depolarizing action of GABA (g-aminobutyric acid) on myelinated fibers of peripheral nerves. Morris, M. E.; Di Costanzo, G. A.; Fox, S.; Werman, R. (Dep. Anaesth., Univ. Toronto, Toronto, ON M5S 1A8, Can.). Brain Res., 278(1-2), 117-26 (English) 1983. CODEN: BRREAP. ISSN: 0006-8993. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) In initial in vivo observations, i.v. injections of GABA [56-12-2] increased the excitability of the low-threshold, fast-conducting fibers of the superficial radial and median nerves of the cat. Similar, graded, reversible effects were confirmed (using changes in the amplitude/integral of the stimulus-evoked A-fiber submaximal compd. action potential to assess excitability) in in vitro studies with the isolated, desheathed frog (Rana pipiens) sciatic nerve. GABA increased the half-maximal action potential of 29.8%, with an ED50 value of 0.09 mM and Hill coeff. of 0.70. This effect did not appear to desensitize, and could be reversibly antagonized by both bicuculline and picrotoxin. Comparison of agonist sensitivities showed a rank order of potency with muscimol [2763-96-4] > 3-aminopropanesulfonic acid [3687-18-1] > GABA > b-guanidinopropionic acid [353-09-3] > imidazole-acetic acid [645-65-8] > guanidoacetic acid [352-97-6] > d-aminovaleric acid [660-88-8]. Structure-activity anal. showed that maximal activity was related to a N+-C sepn. of ~5 ?. Partial substitution of Cl- in the superfusate by isethionate reversibly depressed the effect of GABA. Evidently, extrasynaptic receptors for GABA are present on the myelinated axons of peripheral nerves.

The inhibitory chloride channel activated by glutamate as well as g-aminobutyric acid (GABA)

The inhibitory chloride channel activated by glutamate as well as g-aminobutyric acid (GABA). Single channel recordings from crayfish muscle. Franke, C.; Hatt, H.; Dudel, J. (Physiol. Inst., Tech. Univ. Muenchen, Munich 8000/40, Fed. Rep. Ger.). J. Comp. Physiol., A, 159(5), 591-609 (English) 1986. CODEN: JCPADN. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Outside-out and inside-out patches of membrane were excised from different muscles of crayfish (Austropotamobius torrentium) and single channel currents elicited by synaptic transmitters and their analogs were measured with the patch-clamp technique. If the Cl- concn. was high on both sides of the membrane, glutamate [56-86-0], even at concns. <1 mM, elicited low amplitude single channel currents which were identified as Cl- currents. The same channels were also activated by 10 mM GABA [56-12-2]. Glutamate and GABA showed competition in activating these inhibitory channels. Amplitude histograms of the single channel currents presented well defined peaks corresponding to 3 channel substates I1, I2, and I3, with conductances of ~g(I1) = 22 pS in high Cl- corresponding to a permeability pCl(I1) = 3.5 ′ 10-14 cm3/s), g(I2) = 2g(I1), and g(I3) = 3g(I1). Glutamate activated preferably state I1, and GABA state I2, but both activated all states at sufficient concn. Distributions of the open times in the different states were plotted and fitted each with 1 or 2 exponentials described by time consts. of t(I1) of 1 and 6 ms, t(I2) of 2 to 3 ms, and t(I3) of 1 to 2 ms. The burst durations had components of 3-4 and of 30-40 ms. All these durations were approx. the same when the channels were activated by glutamate and GABA. Quisqualate [52809-07-1] and b-guanidino propionic acid [353-09-3] also elicited the resp. patterns of states of the inhibitory channel. Quisqualate is by far the most effective agonist and glutamate is more effective than GABA at the inhibitory receptor. Picrotoxin blocked activation of the inhibitory channel by GABA more effectively than by glutamate. The importance of the activation of the inhibitory channel by glutamate as well as by GABA and their analogs is discussed. Elements of a tentative reactions scheme are proposed.