Glycine activation of human homomeric α1 glycine receptors is sensitive to pressure in the range of the high pressure nervous syndrome

Abstract

The effect of hyperbaric pressure on the inhibitory glycine receptor has been investigated in voltage-clamped Xenopus oocytes microinjected with cRNA encoding the human α1 glycine receptor subunit. Heterologous expression of the human α1 subunit generated functional glycine-gated channels with properties typical of native receptors. Glycine elicited a concentration-dependent inward current which reversed polarity at −25 mV and was antagonised by nanomolar concentrations of strychnine. Concentration-response curves established for the homomeric α1 glycine receptor at 5, 10 and 15 MPa were progressively shifted to the right with respect to the concentration response curve established at atmospheric pressure (0.1 MPa). Pressure had no effect on the maximal response. The EC 50 values at 0.1, 5, 10 and 15 MPa were 190 μM, 222 μM, 338 μM and 482 μM, respectively. The results demonstrate that a receptor comprised solely of the human α-subunit is sensitive to pressure in the range that affects divers and at which the native rat spinal cord receptor is affected. This finding is discussed in the cortext of the postulated binding sites for glycine and the implications for the design of drugs to protect divers from the effects of pressure.