Born June 8

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About us

Department of Ion Channels has been established in 1994 at the newly founded Institute of Biophysics (former Central Laboratory of Biophysics) at Bulgarian Academy of Sciences. Our founder, master and leader Professor Kiril Boev was the first in Bulgaria to employ electrophysiological studies of smooth muscle preparations, including patch-clamp experiments on single cells. He had invented and designed the double sucrose-gap set-up in the early 70thies. At that time he was a Research scientist at the Institute of Physiology, Department of Vegetative Regulations, from where he eventually moved to the Institute of Biophysics with his team.

Field of interest and research topics

Our scientific interests are focused on the mechanisms of electro-mechanical and pharmaco-mechanical coupling in smooth muscles. Our studies implement registration of contractile activity of smooth muscle preparations, observing and recording the changes in the membrane potential and biophysical properties of transmembrane ionic currents, expressed by single smooth muscle cells under various experimental conditions. Thus, we expose cells to different biologically active substances in order to observe their effects on cellular excitability and tissue contractility, and then we try to figure out how and why did it happen. In search of the most plausible explanations we sometimes benefit from the help of our foreign collaborators, who possess some resources facilitating the monitoring of the dynamics of intracellular calcium movements, or assessing the molecular changes in intracellular proteins and second messengers.

            During the last 5 years our team has been exploring some particular fields of interest as follows:

1.1. Studies on biophysical properties of various potential- and calcium-sensitive potassium channels in vascular smooth muscle cells. These comprise studies of selectivity, conductivity, kinetics, time-, voltage- and calcium dependence of activation and inactivation constants of potassium channels of different types. Some of them are expressed in arteries engaged in thermal homeostasis (rat tail artery); others are responsible for supplying principal organs with blood (basilar artery, coronary arteries, renal arteries, portal vein). The results obtained in these studies are obligatory prerequisite of our further research. That is why each study of the physiology of a particular vessel or organ starts with collecting biophysical data on ion channel properties.

            1.2. Studying changes in the contractile activity and ionic currents of vascular and gastrointestinal smooth muscles under the influence of various endogenous biologically active substances, participating in tissue adaptation to stress factors.

            Those comprise:

            А) In vivo models of oxidative stress, in which we follow up the alterations in intracellular antioxidative defense, including the enzymes that produce endogenous pro-oxidants (heme oxygenase, nitric oxide synthase). We also study the effects of heme oxygenase products on contraction and ionic currents of various smooth muscles and investigate the mechanisms by which these substances accomplish their actions on cellular level.

            B) Studies on the mechanisms by which stress-related hormones like corticotropin-releasing factor, urocortin, thyrotropin-releasing hormone, oxytocin, ghrelin exert their physiological actions on mechanical activity and cellular excitability of vascular and gastro-intestinal smooth muscles. 

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Whole-cell and single-channel voltage clamp, registration of contractions in native and skinned smooth muscles, contraction measurements in resistant vessels (Mulvany’s myography), fluorescent imaging of living cells, intracellular perfusion (Kostyuk’s method).

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1) D.B. Duridanova, P.S. Petkova-Kirova, L.T. Lubomirov, H. Gagov, K.K. Boev (1999) Corticotropin-releasing hormone acts on guinea-pig ileal smooth muscle via protein kinase A. Pflugers Arch. - Eur. J. Physiology 438: 205-212.

2) P.S. Petkova-Kirova, H.S. Gagov, D.B. Duridanova (2000) Urocortin hyperpolarizes stomach smooth muscle via activation of Ca²⁺-sensitive K⁺ currents. J Muscle Res Cell Motil. 21: 639-645.

3) P. Petkova-Kirova, H. Gagov, U. Krien, D. Duridanova, T. Noack, R. Schubert (2000) 4-Aminopyridine affects rat arterial smooth muscle BKCa current by changing intracellular pH. Brit. J. Pharmacol. 131: 1643-1650.

4) P.S. Petkova-Kirova, Lubomirov LT, Gagov HS, Duridanova DB (2000) Superficial Ca²⁺ stores are involved in the effect of thyrotropin-releasing hormone on the K-Ca channel activity in smooth muscle cells of the gastric fundus. Neurophysiology+ 32 (3): 196-197.

5) P.S. Petkova-Kirova, L.T. Lubomirov, H.S. Gagov, V.B. Kolev, D.B. Duridanova (2001) Thyrotropin-releasing hormone activates K⁺ channels in smooth muscle via intracellular Ca²⁺ release. Gen. Physiol. Biophys. 20(1):43-60.

6) F. Fusi, S. Saponara, H. Gagov, G. Sgaragli (2001) Effects of some sterically hindered phenols on whole-cell Ca²⁺ current of guinea-pig gastric fundus smooth muscle cells. Br. J. Pharmacol. 132: 1326-1332.

7) F. Fusi, S. Saponara, H. Gagov, G. Sgaragli (2001) 2,5-Di-t-butyl-1,4-benzohydroquinone (BHQ) inhibits vascular L-type Ca²⁺ channel via superoxide anion generation. Br. J. Pharmacol. 133: 988-996.

8) R. Schubert, U. Krien, H. Gagov (2001) Protons inhibit the BK_Ca channel of rat small artery smooth muscle cells. J. Vasc. Res. 38 (1): 30-38.

9) G.V. Petkov, F. Fusi, S. Saponara, H.S. Gagov, G-P. Sgaragli, K.K. Boev (2001) Characterization of voltage-gated calcium currents in freshly isolated smooth muscle cells from rat tail main artery. Acta Physiol. Scand. 173 (3): 257-265.

10) L. Lubomirov, H. Gagov, P. Petkova-Kirova, D. Duridanova, V. Kalentchuk, R. Schubert (2001) Urocortin relaxes rat tail arteries by a PKA-mediated reduction of sensitivity of the contractile apparatus for calcium. Brit. J. Pharmacol. 134:1564-1570.

11) T. Christova, D. Duridanova, A. Braykova, M. Setchenska, T. Bolton (2001) Heme oxygenase is the main protective enzyme in rat liver upon 6-day administration of cobalt chloride. Arch. Toxicol. 75: 445-451.

12) T.Y. Christova, D.B. Duridanova, M.S.Setchenska (2002) Enhanced heme oxygenase activity increases the antioxidant defense capacity of guinea pig liver upon acute cobalt chloride loading: comparison with rat liver. Comp. Biochem. Physiol. C. 131: 177-184.

13) B. Kadinov, D. Itzev, H. Gagov, T. Christova, T.B. Bolton, D. Duridanova (2002) Induction of heme oxygenase in guinea-pig stomach: role in contraction and single smooth mucle cells ionic currents. Acta Physiol. Scand. 175(4): 297-313.

14) T.Y. Christova, G.A. Gorneva, S.I. Taxirov, D.B. Duridanova, M.S. Setchenska (2003) Effect of cisplatin and cobalt chloride on antioxidant enzymes in the livers of Lewis lung carcinoma-bearing mice: protective role of heme oxygenase. Toxicol. Lett. 138: 235-242.

15) H. Gagov, B. Kadinov, K. Hristov, K. Boev, D. Itzev, T. Bolton, D. Duridanova (2003) Role of constitutively expressed heme oxygenase-2 in the regulation of guinea pig coronary artery tone. Pfluegers Archiv-Eur. J. Physiol. 446: 412-421.

16) R. Ahdut-Hacohen, D. Duridanova, H. Meiri, R. Rahamimoff (2004) Hydrogen ions control synaptic vesicle ion channel activity in Torpedo electromotor neurons. J. Physiol. 556(2): 347-352.

17) R. Schubert, U. Krien, I. Wulfsen, D. Schiemann, G. Lehmann, N. Ulfig, R. Veh, J. Schwarz, H. Gagov (2004) Nitric oxide donor sodium nitroprusside dilates rat small arteries by activation of inward rectifier potassium channels. Hypertension 43(4): 891-896.

18) K. Hristov, I. Altankova, H. Gagov, K. Boev, T. Bolton, D. Duridanova (2004) Calcium-dependent changes in potassium currents of the guinea-pig coronary artery smooth muscle cells after acute cobalt loading in vivo. Pfluegers Arch. – Eur. J. Physiol. 449: 16-25.

19) K. Hristov, H.S. Gagov, D. Itzev, D.B. Duridanova (2004) Heme oxygenase-2 products activate I_KCa: role of CO and iron in guinea pig portal vein smooth muscle cells. J. Muscle Res. Cell Motil. 25: 411-421.

20) D.B. Duridanova, H.S. Gagov, T.B. Bolton (2005) HO-1 induction in the guinea-pig stomach: protection of smooth muscle functional performance during cobalt-induced oxidative stress. Cell. Mol. Biol. 51:495-506.