The subject of this proposal is the relationship between contraction of vascular smooth muscle and concurrent changes in potassium transport across the cell membrane. In particular, this investigation focuses on the specific ion transport processes responsible for the increase in potassium and chloride transport out of smooth muscle cells when they are stimulated to contract. The preliminary data indicate that the majority of this ion transport does not occur via ion channels. Instead, the predominant pathway for potassium efflux is dependent on the presence of chloride and inhibited by loop diuretics. These two features are strong evidence that this pathway represents some form of cotransport. Studies to identify and characterize this transport system are outlined. The functional importance of this ion transporter will be evaluated by assessing whether interruption of the system limits the ability of arteries to contract. The preliminary studies also demonstrate that there is a tight link between intracellular calcium and activation of the potassium transport process. Thus, the final phase of this study will examine the relationship between intracellular calcium and activation of the potassium transport process. Thus, the final phase of this study will examine the relationship between intracellular calcium concentration and activity of the cotransport system. This objective includes an evaluation of potassium cotransport in cultured vascular smooth muscle cells. Achievement of this objective will set the stage for more detailed studies of the regulation of this ion transport system. The studies are important and relevant for two primary reasons. First, this investigation will advance our understanding of how monovalent ion transport systems participate in regulation of the vascular system. Second, these studies have immediate and direct bearing on our understanding and rationale for treatment of hypertension and other cardiovascular disease processes.
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| Warden, D H; Croatt, A J; Katusic, Z S et al. (1999) Characterization of acute reversible systemic hypertension in a model of heme protein-induced renal injury. Am J Physiol 277:F58-65 |
