On the pharmacology of the glycine receptors on the cuneo‐thalamic relay cells in the cat

Abstract

Summary1. In cats either decerebrated or anaesthetized with sodium pentobarbitone, strychnine released by iontophoresis from electrodes containing a 5 mm solution in 165 mm of NaCl, abolished the action of glycine and f3-alanine on cuneo-thalamic relay cells without disturbing their response to equally effective applications of y-aminobutyric acid (GABA) and i3-guanidino-propionic acid.2. The loss of glycine sensitivity appeared to increase as long as the strychnine release continued until even the largest currents tolerated by the electrode were unable to eject effective amounts of glycine. Parallel shifts of the glycine log-current response curves, equivalent to an equipotent dose-ratio of about 2-0 only occurred when the duration of the strychnine applications by current in excess of 28 nA was restricted to a few minutes. 3. Without modifying either the frequency of the spike discharge or the amplitude or shape of the action potential, currents larger than 28 nA occasionally caused a loss of GABA sensitivity. 4. Strychnine administered either intravenously (02 mg/kg) or applied topically to the surface of the cuneate (05 mM) blocked the response to glycine without any obvious effect on the response to GABA. 5. It was concluded that the discovery of a strychnine-sensitive component of the inhibitory potentials recorded from the cuneate nucleus will reveal the physiological role of the glycine receptors on cuneo-thalamic relay cells.

On the pharmacology of ascending, descending and recurrent postsynatic inhibition of the cuneo‐thalamic relay cells in the cat

“…Two columns of post-stimulus histograms recorded before and near the end of the strychnine application show the synaptically evoked inhibition not to be impaired during the marked reduction in glycine sensitivity. Although in the previous paper (Kelly & Renaud, 1973b) glycine was shown to be invariably blocked by small doses of strychnine, on no occasion was the synaptic inhibition seen to be modified by strychnine in maximal doses applied by either iontophoresis 28 to 112 nA, topical application of glycine and transynaptically. Action potentials and histograms from a touch cell identified by antidromic invasion from the medial lemniscus.…”

“…During a longer application of strychnine 28 nA lasting nearly 9 min there was a reversible parallel shift of the glycine log-dose response to the right, equivalent to an equipotent dose-ratio of 3-2 (see Fig. 3, Kelly & Renaud, 1973b) and recovery of full glycine sensitivity took at least 6 minutes. Two columns of post-stimulus histograms recorded before and near the end of the strychnine application show the synaptically evoked inhibition not to be impaired during the marked reduction in glycine sensitivity.…”

“…In view of our finding that iontophoretic glycine was exquisitely sensitive to strychnine (Fig. 1, this paper; Kelly & Renaud, 1973b) when the dose was approximately one fifth to one tenth of that which failed to influence synaptic inhibition, it is unlikely that glycine can play even a minor role in the inhibitory pathway which impinges on relay cells of the cuneate nucleus. The possibility remains, however, that the failure of strychnine to block synaptic inhibition is a consequence of much higher concentrations of glycine occurring in the synaptic cleft than can be mimicked by iontophoresis.…”

“…Curtis, 1962) are usually sufficient to abolish strychnine-sensitive inhibition in the spinal cord (Bradley, Easton & Eccles, 1953) and medulla (Kidokora, Kubota, Shuto & Sumino, 1968; Morimoto, Takata & Kawamura, 1968). Since large doses of strychnine can be less specific and interact with GABA and glycine in the spinal cord (Davidoff, Aprison & Werman, 1969) and not infrequently in the cuneate nucleus (Kelly & Renaud, 1973b), it must be of significance that synaptic inhibition was quite unaffected by iontophoretic applications of strychnine in excess of 100 nA and repeated intrav-enous injections, whose cumulative dose often exceeded 2 mg/kg. The GABA/strychnine interaction which was reported in the preceding paper (Kelly & Renaud, 1973b) must therefore only occur rarely or at extrajunctional sites where the GABA receptors are not involved in synaptic transmission.…”

On the pharmacology of the γ‐aminobutyric acid receptors on the cuneo‐thalamic relay cells of the cat

“…In the second paper (Kelly & Renaud, 1973a) glycine is shown to be selectively blocked by extremely small and short iontophoretic applications of strychnine. The third paper (Kelly & Renaud, 1973b) describes the influence of bicuculline, picrotoxin and strychnine on the duration and intensity of inhibition of cuneothalamic relay cells. Some of our results have been briefly reported (Kelly & Renaud, 1971).…”