Excitable Structures

Head of Department

Corr. Memb. Prof. Andon Kossev, DSc

  • E-mail: kossevbio.bas.bg
  • Phone: (359 2) 9793702
  • Fax: (359 2) 8723787
  • Address: “Acad. G. Bonchev” Str., Block 23, Room 219
    Sofia 1113, Bulgaria


  • Prof. Diana Petkova, DSc., dianaobzor.bio21.bas.bg
  • Prof. Diana Stephanova, DSc, dstephbio.bas.bg
  • Assoc. Prof. Alexander Alexandrov, PhD, physicist, alexbio.bas.bg
  • Assoc. Prof. Mariya Daskalova, PhD, madrasbio.bas.bg
  • Senior Assist. Prof. Daniela Dimitrova, PhD, daniadimyahoo.com
  • Senior Assist. Prof. Teodora Vukova, PhD, tivukovabio.bas.bg
  • Senior Assist. Prof. Vladimir Dimitrov, PhD, vgdiabv.bg
  • Senior Assist. Prof. Kapka Mancheva, PhD, kapka_manchevaabv.bg
  • Boris Andreev, Technical Assistant, borisandreevbio.bas.bg

Main research topics

Relationship between intra- and extracellular action potentials of excitable cells: isolated muscle fibres, axons and neurons and estimation of their functional state (electrical, mechanical and enzyme activity) under physical and chemical influences. Experimental and model investigations of the peculiarities of the extracellular potential field generated by single muscle fibres, motor units and synchronized compound muscle action potentials. Association between the muscle structure and the generated myoelectric activity. Single motor unit activity in health and disease and their relevance to the function of the whole muscle. Fatigue of muscle fibres, motor units and whole muscle. Electromyographic assessment of the muscle functional state. Integrative of the neuromuscular system: sensory-motor integration, motor control in health and disease.

Biophysics and mathematical modeling of complex systems – the excitability structures in the human body. Numerical simulations giving an objective interpretation on the abnormalities of the membrane properties in hereditary, chronic and acquired demyelinating neuropathies and neuronopathies in the peripheral nerve system.

Mechanisms of electro-mechanical and pharmaco-mechanical coupling in smooth muscles. Studies implement registration of contractile activity of smooth muscle preparations, recording and analysing the changes in the membrane potential and biophysical properties of transmembrane ionic currents (channels), expressed by single smooth muscle cells.
Neurotransmitter interactions and neuromodulatory role of neuropeptides in normal and pathological conditions.

Experimental Methods

Recording of intra- (microelectrode technique) and extracellular action potentials and muscle fibre contractions, spectro photometry, selective intramuscular recording of single muscle fibers and motor unit potentials, selective surface motor unit action potential measurements, invasive and surface electromyography during isometric contractions and movements, transcranial magnetic stimulation.

Whole-cell voltage-clamp and current-clamp in single smooth muscle cells, registration of contractions in native and skinned smooth muscles, contraction measurements in resistant vessels (Mulvany’s myography), fluorescent imaging of second messengers in living cells.
In vivo brain microdialysis combined with HPLC detection of aminoacids (Asp,Glu,GABA, taurine).

Mathematical Methods

Simulations of double cable model and multi-layered model of the myelin sheath of human motor and sensory nerve fibres.

Research projects

  1. A bilateral project funded by BAS, Bulgaria and CNR, Italy between IBPhBME, BAS and University of Florence and  “Nello Carrara” Institute of Applied Physics, Italy , 2010-2012.
  2. Joint project 29/4/10 between IBPhBME BAS and Medical University Varna, 2010-2012.
  3. Bulgarian National Science Fund, Project № DТК 02/35, 2010-2012.
    Coordinator: Assoc. Prof. K. Kolikov
  4. Alexander von Humboldt Foundation , 3.3-RKS-BUL/1114309, 2006-2007.
  5. Motor cortex excitability in health and disease
    Institute partnership program of Alexander von Humboldt Foundation between the Institute of biophysics of Bulgarian Academy of Sciences and the Neurology Clinic of Medical University of Hannover (MHH), 2003-2006.
  6. Swiss NSF Institutional Partnership Project № 7 IP 65642 (Program SCOPES): Establishing CSE in Bulgaria and Macedonia, 2002-2004.
  7. Ghrelin-dependent modulation of contraction and membrane ionic currents in resistant arteries
    Bulgarian National Science Fund, Grant  No 1407/2004, 2004-2009
    Coordinator: Prof. D. Duridanova and Prof. A. Kossev
  8. Corticospinal motor excitability changes preceding reaction time movement
    Bulgarian National Science Fund, Grant  No 1407/2004, B-1505/05, 2005-2009.
  9. Electrogenesis of human myelinated and demyelinated nerve fibres: mathematical modeling
    Bulgarian National Science Fund, № К – 806/98, 1998-2001.
  10. Electrogenesis of human myelinated and demyelinated nerve fibres: mathematical modeling
    Bulgarian National Science Fund, № К – 447/94, 1994-1997.
  11. The molecular basis of nerve excitability in man: a patch clamp of ion channels and pumps in human myelinated axons
    Institute of Neurology, London, grant G900630N from the MRC, 1989-1991.

Selected publications

  1. Косев А., Александров А, Даскалов М. (2012) „Транскраниална магнитна стимулация в норма и патология” (монография); Kossev A., Alexandrov A., Daskalov M. (2012) “Transcranial magnetic stimulation in health and disease. Publishing House of the Bulgarian Academy of Sciences “Prof. M. Drinov” (monographic book) (in press).
  2. Stephanova DI., Krustev SM., Negrev N., Daskalova M (2011) The myelin sheath aqueous layers improve the membrane properties of simulated chronic demyelinating neuropathies, Journal of Integrative Neuroscience 10(1): 105-120.
  3. Stephanova DI., Krustev SM., Daskalova M. (2011) The aqueous layers within the myelin sheath modulate the membrane properties of simulated hereditary demyelinating neuropathies, Journal of Integrative Neuroscience 10(1):89-103.
  4. Petkova-Kirova PS, London B, Salama G, Rasmusson RL, Bondarenko VE. (2011) Mathematical Modeling Mechanisms of Arrhythmias in Transgenic Mouse Heart Overexpressing TNF-α. Am J Physiol Heart Circ Physiol. 2011 Nov 11. (Epub ahead of print)
  5. Stephanova DI., (2010) Comparison of membrane property abnormalities in simulated demyelinating neuropathies and neuronopathies. Compt. Rend. Acad Bulg. Sci, 63(3):435-442.
  6. Polina S. Petkova-Kirova, Radoslav S. Borisov, Daniela Z. Dimitrova, Boris Kadinov, Hristo S. Gagov. (2010) Effects of CORM-3 on guinea pig coronary artery. Compt Rend. Acad. Bulg. Sci, 63(3): 383-390.
  7. Dimitrova DZ, Dimitrov SD, Iliev I, Mladenov MI, Hristov KL, Mihov DN, Duridanova DB, Gagov HS. (2010) Ghrelin signaling in human mesenteric arteries. J Physiol Pharmacol. Aug;61(4):383-90.
  8. Gallasch E., Christova M., Krenn M., Kossev A.R., Rafolt D. (2009) Changes in motor cortex excitability following training of a novel goal-directed motor task.  Eur. J. Appl. Physiol., 105(1):47-54.
  9. Kirilov G, Zacharieva S, Alexandrov AS, Lozanov V, Mitev V (2009) Increased plasma endothelin level as an endothelial marker of cardiovascular risk in patients with active acromegaly: a comparison with plasma homocysteine. Methods Find Exp Clin Pharmacol. 31(7):457-61.
  10. Mileva K.N., Bowtell J.L., Kossev A.R.(2009) Effects of low frequency whole body vibration on motor evoked potentials in healthy men. Exp. Physiol., 94(1):103-116.
  11. Schrader C., Peschel T., Däuper J., Rollnik J.D., Dengler R., Kossev A. (2008) Changes in processing of proprioceptiv information in Parkinson’s disease and Multiple System Atrophy. Clin. Neurophysiol., 119:1139-1146.
  12. Schrader C., Siggelkow S., Rollnik J.D., Kossev, A.R. (2008) Impaired proprioception in amyotrophic lateral sclerosis – A study using muscle vibration and transcranial magnetic stimulation. Klin. Neurophysiol., 39(4):262-266.
  13. Schrader C., Peschel T., Kossev, A.R. (2008) Verarbeitung von propriozeptiver Information beim idiopathischem Parkinson-Syndrom und der Einfluss von Levodopa. Klin. Neurophysiol., 39:194-200.
  14. Christova L., Georgieva B, Koryak Yu.A., Kozlovskaja I. B., Kossev A. (2008) Muscle functional state assessment by estimation of muscle conduction velocity. Human Physiology, 34(6):742–747.
  15. Stephanova D, Daskalova M. (2008) Differences between the channels, currents and mechanisms of conduction slowing/block and accommodative processes in simulated cases of focal demyelinating neuropathies. Eur. Biophys. J., 37(6):829-842.
  16. Stephanova D, Daskalova M. (2008) Membrane property abnormalities in simulated cases of mild systematic and severe focal demyelinating neuropathies. Eur. Biophys. J., 37(2):183-195.
  17. Dimitrova D., Georgiev O., Valkova C., Atanasova B., Karagyozov L (2008) Limited variability of CTG/CAG repeats in Lycopersicon nuclear DNA. Biologia plantarum, 52(1): 149-152.
  18. Mladenov MI, Hristov KL, Dimitrova DZ, Schubert R, Lubomirov LT, Gjorgoski IK,  Duridanova DB, Gagov HS (2008). Ghrelin signalling in guinea-pig femoral artery smooth muscle cells. Acta Physiol (Oxf).194(3): 195-206.
  19. Petkova-Kirova P, Rakovska A, Zaekova G, Ballini C, Corte LD, Radomirov R, Vagvolgyi A  (2008) Stimulation by neurotensin of dopamine and 5-hydroxytryptamine (5-HT) release from rat prefrontal cortex: Possible role of NTR1 receptors in neuropsychiatric disorders. Neurochem Int., 53 (6-8): 355-361.
  20. Petkova-Kirova P, Rakovska A, Corte LD, Zaekova G, Radomirov R, Mayer A (2008) Neurotensin modulation of acetylcholine, GABA, and aspartate release from rat prefrontal cortex studied in vivo with microdialysis. Brain Res Bull., 77(2-3):129-35.
  21. T. Vukova, M. Vydevska-Chichova, N. Radicheva. (2008). Fatigue-induced changes in muscle fiber action potentials estimated by wavelet analysis, JEK 18:397-409.
  22. T. Vukova, V. Dimitrov, N. Radicheva. (2008)Three methods for estimation of changes in frequency characteristics of potentials elicited by long-lasting (fatiguing) activity of isolated muscle fibres. Gen Physiol Biophis 29: 243-253.
  23. Stephanova DI, Daskalova M, Alexandrov AS. (2007) Channels, currents and mechanisms of accommodative processes in simulated cases of systematic demyelinating neuropathies. Brain Research, 1171:138-151.
  24. Stephanova DI, Alexandrov AS, Kossev A, Christova L. (2007) Simulating focal demyelinating neuropathies: membrane property abnormalities. Biol. Cybern. 96:195-208.
  25. Christova L, Stephanova D, Kossev A (2007) Branched EMG electrodes for stable and selective recording of single motor unit potentials in humans. Biomed. Tech.52:117-121.
  26. Vydevska-Chichova M, Mileva K, Radicheva N (2007) Differential changes in myeloelectric characteristics of slow and fast fatigable frog muscle fibres during long-lasting activity J. Electromyogr. Kinesiol. 17:131-141.
  27. Dimitrova DZ, Mihov DN, Wang R, Hristov KL, Rizov LI, Bolton TB, Duridanova DB (2007) Contractile effect of ghrelin on isolated guinea-pig renal arteries. Vascul. Pharmacol. 47(1): 31-40.
  28. Alexandrov, AS, Christova LG, Daskalov MN, Kossev AR, Dengler R, Ishpekova BA. (2006) Vergleichende Analyse zwischen residualer Latenz und distaler motorischer Latenz bei diabetischer und alkoholischer Polyneuropathie Klin Neurophysiol 37, 13-15.
  29. Stephanova DI, Daskalova M, Alexandrov AS (2006) Differences in membrane properties in simulated cases of demyelinating neuropathies. Internodal focal demyelination with conduction block. Journal of Biological Physics 32:129-144.
  30. Stephanova DI, Alexndrov AS (2006) Simulating mild systematic and focal demyelinating neuropathies: membrane property abnormalities. Journal of Integrative Neuroscience 5:595-623.
  31. Stephanova DI (2006) Excitability and potentials of human fibres in amyotrophic lateral sclerosis: model investigations, In Amyotrophic Lateral Sclerosis: New Research, Editor: Murray CA, Nova Science Publishers Inc, New York, pp.155-178.
  32. Nikolova M, Pondev N, Christova L, Wolf W, Kossev A (2006) Motor cortex excitability changes preceding voluntary muscle activity in simple reaction time task. Eur. J. Appl. Physiol. 98:212-219.
  33. Christova MI, Pondev NG, Christova LG, Wolf W, Dengler R, Kossev AR (2006) Motor cortex excitability during unilateral muscle activity. J. Electromyogr. Kinesiol. 16:477-484.
  34. Mohammadi B, Krampfl K, Petri S, Bogdanova D, Kossev A, Bufler J, Dengler R (2006) Selective and nonselective benzodiazepine agonists have different effects on motor cortex excitability. Muscle & Nerve 33: 778-784.
  35. Petkova-Kirova PS, Gursoy E, Mehdi H, McTiernan CF, London B, Salama G (2006) Electrical Remodeling of cardiac Myocytes from Mice with Heart Failure due to the Over-expression of Tumor Necrosis Factor {alpha}. Am J Physiol Heart Circ Physiol, 290(5):H 2098-107.
  36. Ishpekova BA, Christova LG, Alexandrov AS, Thomas PK (2005) The electrophysiological profile of hereditary motor and sensory neuropathy – Lom. J. Neurology Neurosurgery and Psychiatry 76:875-878.
  37. Vydevska-Chichova M, Mileva K, Todorova R, Dimitrova M, Radicheva N (2005) Slow and fast fatigable frog muscle fibres: electrophysiological and histochemical characteristics. Gen. Physiol. Biophys. 24:381-396.
  38. Stephanova DI, Daskalova M (2005) Differences in potentials and excitability properties in simulated cases of demyelinating neuropathies. Part III. Paranodal internodal demyelination. Clin. Neurophysiol. 116:2334-2341.
  39. Stephanova DI, Daskalova M (2005) Differences in potentials and excitability properties in simulated cases of demyelinating neuropathies. Part II. Paranodal demyelination. Clin. Neurophysiol. 116:1159-1166.
  40. Stephanova DI, Daskalova M, Alexandrov AS (2005) Differences in potentials and excitability properties in simulated cases of demyelinating neuropathies. Part I. Clin. Neurophysiol. 116:1153-1158.
  41. Vukova, T., Atanassov, A., Ivanov, R., Radicheva, N. (2005) Intensity–dependent effects of microwave electromagnetic fields on acetylcholinesterase activity and protein conformation in frog skeletal muscles. Med. Sci. Mon. 11, BR50-BR56.
  42. Rollnik JD, Kommisarov L, Bogdanova D, Krampfl K, Khabirov FA, Kossev A, Dengler R, Bufler J (2004) Triple stimulation technique (TST) in Amyotrophic Lateral Sclerosis. Clin. Neurophysiol. 115:356-360.
  43. Mileva K, Georgieva B, Radicheva N (2003) About the biological effects of high- and extremely high frequency electromagnetic fields (Review article). Acta Physiol. Pharmacol. Bulg. 27:89-100.
  44. Kirilov G, Tomova A, Dakovska K, Kumanov Ph, Shinkov A, Alexandrov AS (2003) Elevated plasma endothelin as an additional cardiovascular risk factor in patients with Cushin’s syndrome. European Journal of Endocrinology 149(6):549-553.
  45. Zaprianova E, Majtenyi K, Deleva D, Mikova O, Filchev A, Sultanov B, Kolyovska V, Sultanov E, Christova L, Kmetska X, Georgiev D (2003) Serum IgG and IgM Ganglioside GM1 Antibodies in Patients with Multiple Sclerosis. J. Clinical Neuroscience 56:144-149.
  46. Kossev A, Siggelkow S, Dengler R, Rollnik JD (2003) Intracortical inhibition and facilitation in paired-pulse transcranial magnetic stimulation: effect of conditioning stimulus intensity on sizes and latencies of motor evoked potentials. J. Clin. Neurophysiol. 20:54-58.
  47. Kossev AR, Schrader C, Dauper J, Dengler R, Rollnik JD (2002) Increased intracortical inhibition in middle-aged humans – a study using paired-pulse transcranial magnetic stimulation. Neurosci. Lett. 333:83-86.
  48. Siggelkow S, Kossev A, Moll C, Däuper J, Dengler R, Rollnik JD (2002) Impaired sensorimotor integration in cervical dystonia – a study using transcranial magnetic stimulation and muscle vibration. J. Clin. Neurophysiol. 19:232-239.
  49. Rollnik JD, Siggelkow S, Moll C, Däuper J, Kossev AR, Dengler R (2001) Die transkranielle magnetische Doppelstimulation zur Beurteilung kortikokortikaler Inhibiotion und Fazilitierung. Klin. Neurophysiol. 32:26-29.
  50. Zaprianova E, Deleva D, Ilinov P, Sultanov E, Filchev A, Christova L, Sultanov B (2001) Serum ganglioside patterns in multiple sclerosis. Neurochemical Research 26(2):95-100.
  51. Stephanova DI (2001) Myelin as longitudinal conductor: a multi-layered model of the myelinated human motor nerve fibre. Biol Cybern. 84:301-308.
  52. Christova P, Kossev A (2001) Human motor unit recruitment and derecruitment during long lasting intermittent contractions. J. Electromyogr. Kinesiol. 11:189-196.
  53. Kossev A, Siggelkow S, Dengler R, Rollnik JD (2001) Crossed effects of muscle vibration on motor-evoked potentials. Clin. Neurophysiol. 112:453-456.
  54. Lubomirov L, Gagov H, Petkova-Kirova P, Duridanova D, Kalentchuk VU., Schubert R (2001) Urocortin relaxes rat tail arteries by a PKA-mediated reduction of sensitivity of the contractile apparatus for calcium. Br. J. Pharmacol. 134: 1564-1570.
  55. Petkova-Kirova PS, Lubomirov LT, Gagov HS, Kolev VB, Duridanova DB. (2001) Thyrotropin-releasing hormone activates KCa channels in gastric smooth muscle via intracellular Ca2+ release. Gen. Phys. Biophys. 20(1): 43-60.
  56. Kristev I, Christova P, Christova L, Kossev A (2000) Branched surface EMG electrodes and measurement of propagation velocity of excitation along muscle fibers. Biomed. Techn. 45 (Ergänzungsband 2):233-239.
  57. Christova L, Wolf W, Dimitrova M, Christova P, Kossev A (2000) Modulation of single motor unit discharge pattern during the premovement period. Biomed. Techn. 45 (Ergänzungsband 2):223-227.
  58. Peshev R, Christova L (2000) Study of Bovine herpes virus 1 spreading among buffalo hears in Bulgaria. Acta virologica, 44:229-230.
  59. Stephanova DI, Mileva K (2000) Different effects of blocked potassium channels on action potential, accommodation, adaptation and anode break excitation in human motor and sensory myelinated nerve fibres: computer simulations. Biol. Cybern. 83:161-167.
  60. Petkova-Kirova PS, Gagov HS, Duridanova DB. (2000) Urocortin hyperpolarizes stomack smooth muscle via activation of Ca2+ -sensitive K+ currents. J Muscle Res Cell Motil. 21(7): 639-645.
  61. Petkova-Kirova P., Gagov H., Krien U., Duridanova D., Noack T., Schubert R. (2000) 4-Aminopyridine affects rat arterial smooth muscle BKCa currents by changing intracellular pH. Br. J. Pharmacol. 131(8): 1643-1650.
  62. Aleksandrov AS, Christova LG (1999) Comparison between normal and Parkinsonian patern of motor unit firing. Electormyography and Clinical Neurophysiology 39(8):469-472.
  63. Christova LG, Alexandrov AS, Ishpekova BA (1999) Single motor units activity pattern in patients with Schwartz-Jampel syndrome. J. Neurol. Neurosurg. Psych. 66:252-253.
  64. Ivanov R, Georgieva B, Naumova P, Mileva K, Radicheva N (1999) Influence of a Protein Hydrolysate from Green Algae on the Activity of Some ATPase Systems in Frog Skeletal Muscle. Methods Find. Exp. Clin. Pharmacol. 21(5):339-343.
  65. Radicheva N, Mileva K, Stoyanova N, Georgieva B (1999) Further Studies on Nivalin P – Induced Changes in Muscle Fibre Membrane Processes. Methods Find. Exp. Clin. Pharmacol. 21(1) :5-10.
  66. Christova P, Kossev A, Kristev I, Chichov V (1999) Surface EMG recorded by branched electrodes during sustained activity. J. Electromyogr. Kinesiol. 9:263-276.
  67. Kossev A, Siggelkow S, Schubert M, Wohlfarth K, Dengler R (1999) Muscle vibration: different effects on transcranial magnetic and electrical stimulation. Muscle and Nerve 22:946-948.
  68. Mileva K, Vydevska M, Radicheva N (1998) Stretch- and stimulation frequency-induced changes in extracellular action potentials of muscle fibres during continuous activity. J.  of  Muscle Physiol. and Cell Mot. 19:95-103.
  69. Christova P, Kossev A, Radicheva N (1998) Discharge rate of selected motor units in human biceps brachii at different muscle lengths. J. Electromyogr. Kinesiol. 8: 287-294.
  70. Mileva K, Vydevska M, Radicheva N (1998) Stretch and stimulation frequency-induced changes in extracellular action potentials of muscle fibres during continuous activity. J. Musc. Physiol. Cell Mot. 19:95-103.
  71. Radicheva N, Slavcheva G (1998) Spectral and time domain characteristics of single muscle fibre action potentials during continuous activity extracted from model considerations. Biol. Cybern. 79(5): 427-435.
  72. Kossev A, Christova P (1998) Discharge pattern of human motor units during dynamic concentric and eccentric contractions. Electroenceph. Clin. Neurophysiol. 109: 245-255.

International cooperations

  • University of Florence, Florence, Italy
  • Wright State University, Dayton, USA
  • Medical Center, Boston, USA
  • Institute of Neurology, University College London, UK
  • Sport and Exercise Science Research Centre, London South Bank University, UK
  • Medical School of Hannover, Department of Neurology and Clinical Neurophysiology, Germany


  • 2003 – Diana Stephanova – Award of Bulgarian Ministry of Science and Education
  • 2006 – Mariya Daskalova – Award of Bulgarian Academy of Sciences for young scientists

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