Regulation of Neurotransmitter Receptor Function



Paul Brehm
Paul Brehm
Professor
PhD, UCLA

Fumihito Ono - Research Assistant Professor
Anatoly Shcherbatko - Research Assistant Professor

Neurobiology and Behavior
Life Sciences, 053
Brehm Lab
phone: 632-8635/632-8982
FAX: 632-6661

Ion channels and receptors form the basic elements of electrical signaling in the nervous system. Molecular and physiological studies have shown that specific channel types are members of larger gene families, giving rise to multiple isoforms. The physiological significance of large-scale functional and molecular redundancy in the nervous system is not known. My lab uses Xenopus and Zebrafish animal model systems, as well as heterologous expression systems, to investigate this interesting question. The targets of study include voltage-dependent channels (sodium, calcium and potassium), acetylcholine receptors and thermally activated channels in the peripheral nervous system. Physiological analyses of programmed pre- and post-synaptic function capitalize on the unique advantages offered by study of developing Xenopus. In complementary studies, genetically altered Zebrafish, bearing specific ion channel defects, are used to assign physiological roles to individual receptor/ion channel isoforms. We are currently focusing our efforts on behavioral dysfunction that results from defects located within spinal neurons or at the peripheral synapses.

Relevant Publications:

Naranjo, D. and Brehm P. (1993) Modal shifts in acetylcholine receptor channel gating confer subunit-dependent desensitization Science 260; 1811-1814

Liu, Y. and Brehm P. (1993) Expression of subunit-omitted mouse nicotinic acetylcholine receptors in Xenopus laevis oocytes. J. Physiol. 470;349-363

Shepherd, D. and Brehm (1994) Adult forms of nicotinic acetylcholine receptors are expressed in the absence of nerve during differentiation of a mouse skeletal muscle cell line. Developmental Biology 162; 549-557.

Murray et al. (1994) A single site on the epsilon subunit is responsible for the change in ACh receptor channel conductance during skeletal muscle development. Neuron 14; 865-870.