Billups, Daniela; (2002) Modulation of synaptic transmission by interacting proteins and transporters. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The properties of synaptic transmission may be modulated by transporters which regulate neurotransmitter and ion concentrations, and by proteins which interact with ion channels and transporters. I have investigated this for inhibitory and excitatory synapses in the retina and the cerebellum, using electrophysiological (patch-clamp) techniques. For inhibitory synaptic transmission, I have (1) discovered that GABAC receptors in retinal bipolar cells are modulated by the intracellular cytoskeletal protein MAP-1B, and shown that disrupting the interaction between MAP-1B and the GABAC receptor increases the sensitivity of the receptor to GABA, which is expected to alter the duration of the inhibitory postsynaptic current in these cells; and (2) studied the possibility that chloride transporters maintain a non-uniform intracellular chloride distribution in retinal bipolar cells, which determines the direction and magnitude of the GABA evoked membrane potential changes in the cell. For excitatory synaptic transmission I have (1) studied glutamatergic synaptic transmission in the cerebellum of transgenic mice lacking either of the glutamate transporters GLT-1 or GLAST, and demonstrated that GLAST knockout prolongs the synaptic current at the parallel fibre to Purkinje cell synapse, but that knocking out GLT-1 or GLAST does not alter the mossy fibre to granule cell synaptic current; (2) studied the effect of glycine on mossy fibre to granule cell synaptic transmission in the cerebellum of the rat, showing that the NMDA receptor glycine site is saturated even when no glycine is added to the superfusing solution; and (3) studied the properties of the LIM protein Ajuba, which interacts with the major glial glutamate transporter GLT-1, and shown that Ajuba does not modulate the transporter's glutamate sensitivity, its associated anion channel, or the number of transporters in the plasma membrane.

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