Although GJ-mediated intercellular communication between cells of the vascular wall has, in general, been recognized to play a key role in the coordination of vascular function, the role of GJ in capillary endothelial cells has not yet been completely clarified. Available indirect in vivo evidence implicates capillary GJ participation in capillary-arte-riolar communication and the feedback pathway of local blood flow control. Microvascular endothelial cells grown in vitro retain their ability to respond to vasoactive stimuli and to communicate these responses via gap junctions. Thus, concerted research efforts should be undertaken to provide the necessary direct in vivo evidence to firmly establish participation of capillary GJs in local blood flow control under normal and pathophysiological conditions.


Capillary: The smallest blood vessel (~5 mm in diameter in mammalian tissues) lacking continuous muscular layer.

Electrotonic spread: Passive spread of electrical current (e.g., carried by the ions of the cell cytosol) whose amplitude decays with distance.

Gap junction: Intercellular channel directly connecting the cytosols of two adjacent cells.

Sepsis: Systemic inflammatory response to local infection.


This research was supported by the Canadian Institutes of Health Research and Heart and Stroke Foundation of Ontario.


2. Cai et al. (2001). J. Mol. Cell. Cardiol. 33, 957-967.

3. Dietrich and Tyml (1992). Microvasc. Res. 43, 87-99.

5. Song, H., and Tyml, K. (1993). Evidence for sensing and integration of biological signals by the capillary network. Am. J. Physiol. 265, H1235-H1242.

6. Berg, B. R., Cohen, K. D., and Sarelius, I. H. (1997). Direct coupling between blood flow and metabolism at the capillary level in striated muscle. Am. J. Physiol. 272, H2693-H2700. This paper implies physiological relevance of capillary—arteriolar communication.

7. Collins et al. (1998). Microvasc. Res. 56, 43-53.

8. McGahren, E. D., Beach, J. M., and Duling, B. R. (1998). Capillaries demonstrate changes in membrane potential in response to pharmacological stimuli. Am. J. Physiol. 274, H60-H65. Using a voltage-sensitive dye, this work shows for this first time that capillary endothelial cells can sense pharmacological stimuli in terms of hyper/depolarization of endothelial cells.

9. Beach, J. M., McGahren, E. D., and Duling. B. R. (1998). Capillaries and arterioles are electrically coupled in hamster cheek pouch. Am. J. Physiol. 275, H1489-H1496. Based on measurements of voltage-sensitive dye loaded in capillary endothelial cells in vivo, this work shows for this first time that these cells are electrically coupled.

11. Ouellette et al. (2000). Microvasc. Res. 60, 222-231.

12. Tyml et al. (1998). J. Appl. Physiol. 84, 837-844.

13. Lidington, D., Ouellette, Y., and Tyml, K. (2002). Communication of agonist-induced electrical responses along "capillaries" in vitro can be modulated by lipopolysaccharide, but not nitric oxide. J. Vasc. Res. 39, 405-413. This work demonstrates electrical communication in capillary-like structures grown in vitro.

14. Lidington, D., Ouellette, Y., and Tyml, K. (2000). Endotoxin increases intercellular resistance in microvascular endothelial cells by a tyrosine kinase pathway. J. Cell. Physiol. 185, 117-125.

15. Lidington et al. (2002). J. Cell. Physiol. 193, 373-379.


Gustafsson, F., and Holstein-Rathlou, N. H. (1999). Conducted vasomotor responses in arterioles: Characteristics, mechanisms, and physiological significance. Acta Physiol. Scand. 167, 11-21. Lidington, D., Ouellette, Y., Li, F., and Tyml, K. (2003). Conducted vasoconstriction is reduced in a mouse model of sepsis. J. Vasc. Res. 40, 149-158.

Mitchell, D., Yu, J., and Tyml, K. (1997). Comparable effects of arteriolar and capillary stimuli on blood flow in rat skeletal muscle. Microvasc. Res. 53, 22-32. This paper shows that arteriolar responses to distant capillary pharmacological stimuli cannot be explained by direct diffusion of agents from capillary to arteriole. Saez, J. C., Berthoud, V. M., Moreno, A. P., and Spray, D. C. (1993). Gap junction. Multiplicity of controls in differentiated and undifferentiated cells and possible functional implications. In: Advances in SecondMes-senger and Phosphoprotein Research (S. Shenolikar and A. C. Nairn, eds.), Vol. 27, New York: Raven Press, pp.163-199.

Capsule Bibliography

K. Tyml is a professor at the Department of Medical Biophysics, University of Western Ontario. His research interests include local micro-vascular blood flow control, arteriolar reactivity, and the role of capillaries and vascular cell-to-cell communication in this control. Recently, he has examined the pathophysiological effects of skeletal muscle disuse, and sepsis, and the protective effect of vitamin C, on this local control.

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