Penny Moody-Corbett

DEVELOPMENTAL ACQUISITION OF MEMBRANE EXCITABILITY

In the nervous system cell-cell interactions are mediated through synaptic connections that are specialized in both structure and function. In adults, functional synapses depend upon the appropriate alignment of pre-and post-synaptic elements. Further, activation in the post-synaptic cell depends on the distribution of a second class of membrane proteins, the ion channels which are regulated by membrane potential or second messengers.

The objective of Dr. Moody-Corbett's research has been to understand the developmental acquisition of membrane ion channels in the post-synaptic membrane relative to the development of the synapse. These studies have taken advantage of a simple nerve- muscle culture system prepared from the frog Xenopus laevis. In this preparation it has been possible to examine the acquisition of potassium, sodium and calcium currents in the muscle cells relative to innervation and the acquisition of the receptors to the neurotransmitter acetylcholine.

Dr. Moody-Corbett's results indicate that muscle cells are able to acquire all of the necessary elements for membrane excitation in the absence of innervation. However, innervation regulates the timing and spatial expression of the channels. Research from her lab, together with work from other labs, has indicated that the acetylcholine receptor channels and potassium channels are the first ion channels present in muscle membrane, appearing before the expression of sodium, calcium or chloride channels.

The early expression of potassium and acetylcholine receptor channels assures that the first synaptic contacts will be effective in exciting the post-synaptic membrane, and that this membrane is able to repolarize and maintain a resting potential. Innervation enhances the expression of sodium channels and this, in turn, appears to regulate the further expression of the potassium channels.

In the model used in the lab, it has been possible to demonstrate a localization of sodium channels and an inactivating class of potassium channels closely associated with acetylcholine receptors in early synaptic contacts. This is the first demonstration of a local distribution of potassium channels in the post-synaptic membrane of vertebrate muscle and suggests an important role of these channels in regulating membrane excitability at this site.

In order to further investigate the unique role of potassium channels in excitable membranes we have recently isolated three potassium channel cDNA sequences from Xenopus muscle which correspond to Kv1.2, Kv1.4 and a novel Shaker channel Kv1.10. We will utilize these sequences to further examine the structural and functional properties of the potassium channels in developing and mature