EXPRESSION AND FUNCTION OF GLYCINE-GATED CL- CHANNELS

Glycine is a major inhibitory neurotransmitter in the spinal cord and brain stem. Glycine acts by increasing the Cl- permeability through activation of a specific receptor/ion channel complex consisting of a pentameric subunit assembly. Molecular cloning has disclosed the nature of receptor subunits alpha and beta. While the role of the beta-subunit is still unclear, the alpha-subunit functions in both ligand (agonist/antagonist) binding and ion channel formation. It has been demonstrated that there are two isoforms of the alpha-subunit, alpha(1) and alpha(2). The mRNAs encoding these subunit isomers are transcribed from different genes, in spite of their structural similarity. The alpha(1) mRNA is abundant in adult spinal cord, whereas the alpha(2) mRNA is mainly expressed in developing spinal cord as well as various regions of brain tissue. The single channel properties were examined in outside-out patches excised from Xenopus oocyte membrane expressing alpha(1) or alpha(2) homomeric receptors. The mean open time of alpha(2) channels was 70-times longer than that of alpha(1) channels. The subunit switching from alpha(2) to alpha(1), and resulting shortening of channel kinetics, may ensure a rapid motor control in adult animals.