PubMed · 2639371
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1989. [Psychophysiological tests].. https://pubmed.ncbi.nlm.nih.gov/2639371/
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The amino acids glycine, beta-alanine and taurine are all endogenous agonists of the glycine receptor. In this study, a combination of rapid agonist application onto macropatches and steady-state single-channel recordings was used to compare the actions of glycine, beta-alanine and taurine upon homomeric alpha1 human glycine receptors transiently expressed in human embryonic kidney (HEK 293) cells. The 10-90 % rise times determined from rapid application of 100 microM of each agonist were indistinguishable, indicating each agonist has a similar association rate. At saturating concentrations (30 mM) the rise time for glycine (0.26 ms) was 1.8-fold faster than that for beta-alanine (0.47 ms) and 3.9-fold faster than that for taurine (1.01 ms), indicating clear differences in the maximum opening rate between agonists. The relaxation following rapid removal of agonist was fitted with a single exponential for beta-alanine (3.0 ms) and taurine (2.2 ms), and two exponential components for glycine with a weighted mean time constant of 27.1 ms. This was consistent with differences in dissociation rates estimated from analysis of bursts, with taurine > beta-alanine > glycine. Exponential fits to the open period distributions gave time constants that did not differ between agonists and the geometric distribution for the number of openings per burst indicated that all three agonists had a significant component of single-opening bursts. Based upon these data, we propose a kinetic scheme with three independent open states, where the opening rates are dependent upon the activating agonist, while the closing rates are an intrinsic characteristic of the receptor.
Phenothiazines are well-known calmodulin inhibitors that interact with many receptors and channels including a variety of potassium channels. In this study, we report a blocking effect of trifluoperazine (TFP) on voltage-gated Kv1.3 channels expressed in human T lymphocytes. Application of TFP in the concentration range from 1 to 20 microM reduced the current amplitude to about a half of the control value. The currents were blocked to less than 0.05 of the control value at 50 microM TFP concentration. The blocking effect was accompanied by a substantial increase in the current inactivation rate, whereas the activation rate and the steady-state activation and inactivation were not changed significantly. The blocking effect of TFP was voltage dependent being most potent at +60mV and least potent at -20mV. The blocking effect of TFP on the currents and the recovery from block was time dependent. Other calmodulin antagonists: tamoxifen (TMX) and thioridazine also inhibited the channels at micromolar concentrations. The effects exerted by TMX and thioridazine resembled the inhibitory effect of TFP. The blocking effect of thioridazine was time dependent and appeared to be more potent that the inhibition by TFP and TMX. TFP, TMX and thioridazine inhibited the activity of Kv1.3 channels only when applied extracellularly. The inhibitory effect of all the compounds was reversible. The possible physiological significance of the current inhibition is discussed.
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