Structural elements controlling subunit specific properties of glutamate-gated ion channels

Glutamate-gated ionotropic channels (iGluR) are essential for the excitatory signal transmission. NMDA and AMPA receptors have a different mode of gating that modulates the channel conductivity and permeability that is central to synaptic transmission. Details of the gating mechanism are not fully understood. Features of some membrane-located amino acids AA for permeability were described previously and in one recent study, the first AA changing the conductivity in NMDA subunits was identified. We use

(i) the single-channel recording and

(ii) whole cell recording to sample structural changes in NMDA/AMPA chimeras by employing various channel modulators and blockers. Acquired data could reveal the key sections that control iGluR subtype specific functions regulating synaptic transmission.

Regulation of glutamate receptor mRNA processing – editing/alternative splicing

AMPA glutamate receptors (AMPAR) are responsible for the primary post-synaptic depolarization. Functional properties of native receptors are governed by four different subunits assembling into tetramers. Little is known about the processes and rules underlying channel assembly. It has been shown that mRNA processing (editing and alternative splicing) of subunits plays also a role in assembly. The major goal of this project is to understand the rules between neuronal activity, mRNA processing and receptor assembly. A better understanding of AMPAR biogenesis helps to explain development and function of excitatory circuits associated with mechanisms of learning and memory.