Department of Pharmacy and Pharmacology

sergey_smirnov

Senior Lecturer in Pharmacology

5 West - 2.44

Email:  S.V.Smirnov@bath.ac.uk

Tel: +44 (0) 1225 384471 

 

Dr Sergey Smirnov 

Profile

The research in the laboratory is focused upon the investigation of membrane and cellular mechanisms regulating the arterial function in physiological conditions and in disease using contemporary laboratory methods which include small vessel myography, electrophysiological patch-clamp technique, molecular biological and imaging techniques.

Arteries determine blood pressure by changing their diameter which is controlled by the activity of ion channels. One group of ion channels ubiquitously present in smooth muscle cells (VSMCs) which compose the arterial wall, K+ channels are central for the regulation of resting membrane potential hence vascular tone. Among them voltage-gated K+ (Kv) channels are abundant in pulmonary arterial SMCs and contribute to an important physiological response to hypoxia termed hypoxic pulmonary vasoconstriction (HPV). We initially demonstrated a significant decrease in Kv channels expression (which would results in membrane depolarization and vasoconstriction) in chronic hypoxia in the rat (Smirnov et al., 1994), an animal model of pulmonary hypertension. Recently, we demonstrated that Kv channels in PASMCs are closely linked to the mitochondrial function via a novel mitochondrial-mediated Mg2+-dependent mechanism (Firth et al., 2008). This unique regulatory mechanism is due to an existence of sub-membrane population of mitochondria in PASMCs and is not present in systemic SMCs (Firth et al., 2009).

In collaboration with colleagues from the Department of Physics we developed a novel approach to investigate protein complexes on the cell surface using atomic and magnetic force microscopy. With this approach we successfully demonstrated distribution of individual endothelin receptor molecules on the surface of aortic SMCs (Moskalenko et al, 2010).

In collaboration with colleagues from the University of Calgary, we showed specific distribution along the renal vascular tree of another type of K channels, the inward rectifier (KIR), and demonstrated their functional importance in renal afferent arterioles which are central for blood pressure control (Chilton et al., 2011).

Publications

Shaifta, Y., Snetkov, V. A., Prieto-Lloret, J., Knock, G. A., Smirnov, S. V., Aaronson, P. I. and Ward, J. P. T., 2015. Sphingosylphosphorylcholine potentiates vasoreactivity and voltage-gated Ca2+ entry via NOX1 and reactive oxygen species. Cardiovascular Research

Garland, C. J., Smirnov, S., Bagher, P., Lim, C., Mitchell, R., Stanley, C., Pinkney, A. and Dora, K.A., 2015. TRPM4 inhibitor 9-phenanthrol activates endothelial cell intermediate conductance calcium-activated potassium channels in rat isolated mesenteric artery. British Journal of Pharmacology, 172 (4), pp. 1114-1123.

Iarova, P. L., Smirnov, S. V., Dora, K. A. and Garland, C. J., 2013. β1-adrenoceptor stimulation suppresses endothelial IKCa-channel hyperpolarization and associated dilatation in resistance arteries. British Journal of Pharmacology, 169 (4), pp. 875-886.

Smirnov, S. V., Loutzenhizer, K. and Loutzenhiser, R., 2013. Voltage-activated Ca2+ channels in rat renal afferent and efferent myocytes: no evidence for the T-type Ca2+ current. Cardiovascular Research, 97 (2), pp. 293-301.

Smirnov, S., Loutzenhizer, K. and Loutzenhiser, R., 2012. Identification of voltage-activated calcium currents in renal afferent and efferent arterioles of the rat. FASEB Journal, 26 (Meeting Abstracts), 675.5.

Chilton, L., Smirnov, S. V., Loutzenhiser, K., Wang, X. and Loutzenhiser, R., 2011. Segment-specific differences in the inward rectifier K+ current along the renal interlobular artery. Cardiovascular Research, 92 (1), pp. 169-177.

Snetkov, V. A., Smirnov, S. V., Kua, J., Aaronson, P. I., Ward, J. P. T. and Knock, G. A., 2011. Superoxide differentially controls pulmonary and systemic vascular tone through multiple signalling pathways. Cardiovascular Research, 89 (1), pp. 214-224.

Moskalenko, A. V., Yarova, P. L., Gordeev, S. N. and Smirnov, S. V., 2010. Single protein molecule mapping with magnetic atomic force microscopy. Biophysical Journal, 98 (3), pp. 478-487.

Yuill, K. H. and Smirnov, S. V., 2010. Calcium-dependent regulation of voltage-gated sodium channels in cardiac myocytes: just the beginning? Cardiovascular Research, 85 (3), pp. 411-412.

Firth, A. L., Gordienko, D. V., Yuill, K. H. and Smirnov, S. V., 2009. Cellular localization of mitochondria contributes to Kv channel-mediated regulation of cellular excitability in pulmonary but not mesenteric circulation. American Journal of Physiology-Lung Cellular and Molecular Physiology, 296 (3), L347-L360.

Beard, J. D., Burbridge, D. J., Moskalenko, A. V., Dudko, O., Yarova, P. L., Smirnov, S. V. and Gordeev, S. N., 2009. An atomic force microscope nanoscalpel for nanolithography and biological applications. Nanotechnology, 20 (44), 445302.

Rahman, M. M., Knock, G. A. and Smirnov, S. V., 2009. Role of voltage-gated K+ channels in pulmonary arteries: The tale of two channels. In: Physiological Society Meeting, 2009-07-07 - 2009-07-10.

Smirnov, S. V., Gordienko, D. V., Firth, A. L. and Yuill, K. H., 2009. Structural and functional association between mitochondria and voltage-gated K+ currents in the rat pulmonary (PAMs), but not mesenteric (MAMs) arterial myocytes. FASEB Journal, 23, 999.7.

El-Awady, M. S. H., Smirnov, S. V. and Watson, M. L., 2009. Voltage-independent calcium channels mediate lipopolysaccharide-induced hyporeactivity to endothelin-1 in the rat aorta. American Journal of Physiology-Heart and Circulatory Physiology, 296 (5), H1408-H1415.

Firth, A. L., Yuill, K. H. and Smirnov, S. V., 2008. Mitochondria-dependent regulation of Kv currents in rat pulmonary artery smooth muscle cells. American Journal of Physiology-Lung Cellular and Molecular Physiology, 295 (1), L61-L70.

Rahman, M. and Smirnov, S., 2008. 4-aminopyridine contracts pulmonary artery in voltage-dependent and voltage-independent manner. pA2Online, 6 (2), 007P.

Firth, A. L., Gordienko, D. V., Yuill, K. H. and Smirnov, S. V., 2008. Cellular localization of mitochondria contributes to the regulation of Kv channel currents in the rat pulmonary, but not mesenteric arterial myocytes. In: Physiological Society Meeting, 2008-12-15 - 2008-12-17.

El-Awady, M. S. H., Smirnov, S. V. and Watson, M. L., 2008. Desensitization of the soluble guanylyl cyclase/cGMP pathway by lipopolysaccharide in rat isolated pulmonary artery but not aorta. British Journal of Pharmacology, 155 (8), pp. 1164-1173.

Smirnov, S. V., Telezhkin, V. S., Firth, A. L. and Yuill, K. H., 2008. Involvement of Na+-H+ exchanger in hypoxia-mediated inhibition of voltage-gated K+ channels in rat small pulmonary arterial myocytes. Fundamental & Clinical Pharmacology, 22 (Suppl 2), p. 63.

El-Awady, M. S. H., Smirnov, S. V. and Watson, M. L., 2008. Lipopolysaccharide-induced vascular hypocontractility to endothelin-1 in rats is dependent on non-voltage-gated calcium channels but not on calcium sensitization. Fundamental & Clinical Pharmacology, 22 (Suppl 2), p. 74.

This list was generated on Tue Oct 17 13:13:56 2017 IST.

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