It is proposed to study the regulation of potassium channel gene expression in two cell types that contribute to cardiovascular function, sympathetic postganglionic neurons and cardiac myocytes. In the peripheral sympathetic nervous system, neurons in paravertebral ganglia have different firing properties compared with those in prevertebral ganglia and this is due in large part to differential expression of voltage-activated potassium channels.
Specific Aims 1 and 3 are directed toward comparing the expression of potassium channel genes in sympathetic neurons in these two classes of ganglia to find which genes are differentially expressed and could therefore contribute to the differentiation of the electrophysiological phenotype.
Specific Aims 2 and 3 will compare potassium channel expression in atrial and ventricular muscle. It is well established that the shape and duration of action potentials are markedly different in atrial and ventricular muscle cells, and much of this differentiation appears to be due to differential expression of voltage-gated potassium channels. We will determine which potassium channel genes are differentially expressed in atrial and ventricular muscle. These studies will provide a molecular framework for understanding how potassium channels contribute to the electrophysiological differentiation of adult tissues and could help develop strategies for finding new potassium channel antagonists with potential therapeutic value as class III anti-arrhythmics.
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