David T. Kurjiaka, Ph.D.

     The goal of my research is to understand the intercellular messages that cells communicate to their neighbors with a particular emphasis on how these messages might be affected by hypertension. Information (electrical and chemical) travels from cell to cell through gap junction channels; paired hexameric proteinhemichannels that form between cells providing a direct intercellular pathway. The nature of the message communicated between cells appears to be dependent upon the identity of the coupled cells. In the vasculature, cell:cell communication coordinates vasomotor responses longitudially along arteriole networks and circumferentially through the numerous layer of smooth muscle cells (SMC) that comprise large arteries.

     At the same time, junctional communication appears essential for the regulation of vascular growth status. Numerous studies on cancer cells have documented a complete loss of junctional communication in cells that have escaped growth constraints. In proliferating vascular SMC, we observed no change in electrical communication whereas chemical permeability (large ions) was dramatically reduced compared with their growth arrested counterparts. This finding was the first to demonstrate that electrical and chemical communication can be independently regulated.

The presence of hypertension leads to an alteration in vasomotor responses that occurs coincident with the growth of vascular smooth muscle cells (SMC).Vascular growth results in a thickening of the blood vessel wall reducing lumenal diameter. Lumenal narrowing increases vasular resistance which furthers the elevated blood pressure and thereby work on the heart. Thus, lumenal narrowing puts people at greater risk for strokes or heart attacks. Whether cell:cell communication is involved in this disease process has not been directly investigated although several studies have shown enhanced gap junction expression in hypertension and atherosclerotic plaques.

My laboratory will approach investigating this question through both in vivo and in vitro techniques in hypertensive hamsters. This includes studying arteriolar vasomotor responses from in vivo hamster microvascular preparations. In these same animals, vascular smooth muscle and endothelial cells will be isolated to determine whether gap junction expression is altered by hypertension.   In addition, we can determine whether the extent of cell:cell communication is altered by hypertension via the dual whole cell voltage clamp technique.  Employing both in vivo and in vitro techniques on the same model system will provide a better understanding of the role gap junctions play in the pathophysiology of hypertension.

Selected References:

• Segal, S.S., D.G. Welsh, and D.T. Kurjiaka. (1999) Spread of vasodilatation and vasoconstriction along resistance microvessels of hamster skeletal muscle. J. Physiol. (Lond.), 516: 283-291.

• Kurjiaka, D.T., T.D. Steele, M.V. Olsen and J.M. Burt. (1998) Gap junction permeability is diminished in proliferating vascular smooth muscle cells. Am. J. Physiol., 275 (Cell Physiol.):C1674-C1682.

• Kurjiaka, D.T. and S.S. Segal. (1996) Autoregulation during pressor response elevates wall shear rate in arterioles. J. Appl. Physiol., 80: 598-604.

• Kurjiaka, D.T. and S.S. Segal. (1996) Blood flow responses to conducted vasodilation in arteriolar network of striated muscle. Am. J. Physiol., 269 (Heart Circ. Physiol.): H1723-H1728.

• Kurjiaka, D.T. and S.S. Segal. (1995) Interaction  betwee n conducted vasodilation and sympathetic nerve activation in hamster cremaster arterioles. Circ. Res., 76: 885-891.

• Segal, S.S., D.T. Kurjiaka and A.L. Caston. (1993) Endurance training increases arterial wall thickness in rats. J. Appl. Physiol., 74: 722-726.