Възбудими структури

Ръководител на секцията

чл.-кор. проф. дбн Андон Косев

  • Email: kossevbio.bas.bg
  • Телефон: (359 2) 9793702
  • Факс: (359 2) 8723787
  • Адрес: ул. “Акад. Г. Бончев”, блок 23, стая 219
    София 1113, България

Състав на секцията

Основни научни направления

Връзка между вътре- и извънклетъчни акционни потенциали на възбудими клетки: изолирани мускулни влакна, аксони и неврони и оценка на функционалното им състояние (електрическа, механическа и ензимна активност) при физически и химически въздействия. Експериментални и моделни изследвания върху спецификата на екстрацелуларното потенциално поле, генерирано от изолирани мускулни влакна, двигателни единици и сумарни синхронизирани мускулни потенциали. Връзка между структурата на мускула и генерираната от него електрическа активност. Активност на отделни двигателни единици в норма и патология и значимостта и за функцията на целия мускул. Умора на мускулни влакна, двигателни единици и цял мускул. Електромиографска оценка на функционалното състояние на мускула. Поведение на нервно-мускулната система като цяло: сетивно-двигателна интеграция, регулация на движенията в здраве и болест.

Биофизика и математично моделиране на сложни системи – възбудимите структури в човешкото тяло. Числени симулации, даващи обективна интерпретация на нарушенията на мембранните свойства при наследствени, хронични и остри демиелинизиращи невропатии и невронопатии в периферната нервна система.

Електромеханичното и фармакомеханичното куплиране в гладки мускули. Оценка на съкратителната активност на гладката мускулатура, регистрация и анализ на мембранния потенциал и биофизичните свойства на трансмембранните йонни токове (канали) в единични гладкомускулни клетки.
Невротрансмитерни взаимодействия и невромодулаторна роля на невропептидите в норма и патология.

Експериментални методи

Регистриране на вътре- (микроелектродна техника) и извънклетъчни акционни потенциали и контракция на изолирани мускулни влакна, спектрофотометрия, селективно вътремускулно записване на потенциали от отделни мускулни влакна и двигателни единици, измерване на потенциалите на отделни двигателни единици чрез повърхности селективни електроди, електромиография по време на изометрични контракции и движения посредством жичкови и повърхностни селективни електроди, транскраниална магнитна стимулация.

Whole cell voltage-clamp и current -clamp в единични гладкомускулни клетки, регистриране на съкратителната активност на нативни и пермеабилизирани гладко-мускулни препарати, измерване на съкращението на резистентни съдове (Mulvany’s myography), флуоресцентно маркиране на вторични посредници в живи клетки.

In vivo мозъчна микродиализа и high pressure liquid chromatography- (HPLC-) определяне на аминокиселини (аспартат, глутамат, гама аминомаслена киселина, таурин).

Математически методи

Симулиране на двойнокабелен модел и на мултиламеларен модел на миелиновата обвивка на човешки моторни и сензорни нервни влакна.

Изследователски проекти

Текущи проекти

Приключили
  1. Проект по двустранната спогодба за научно сътрудничество и обмен на Българската академия на науките между ИБФБМИ,БАН и Университет на Флоренция и Институт по приложна физика “Нело Карара”, Флоренция, Италия, 2010-2012.
  2. Договор 29/4/10 между ИБФБМИ и Медицински Университет – Варна, 2010-2012.
  3. Договор № ДТК 02/35 към ФНИ на МОН с ръководител доц. Кирил Коликов, 2010-2012
  4. Фондация Александър фон Хумболт, 3.3-RKS-BUL/1114309, 2006-2007.
  5. Възбудимост на моторната кора в норма и патология
    Договор за институтско партньорство между ИБФ и Неврологичната клиника на Медицинския университет в Хановер. – Финансиран от Фондацията „Александър фон Хумболт”, 2003-2006.
  6. Swiss NSF Institutional Partnership Project № 7 IP 65642 (Program SCOPES): Establishing CSE in Bulgaria and Macedonia, 2002-2004.
  7. Роля на грелин в модулиране съкратителната активност и мембранните йонни токове в артерии
    Фонд “Научни изследвания”, № 1407/2004, 2004-2009.
    Ръководители: проф. Д. Дуриданова, проф. А. Косев
  8. Промени в кортико-спиналната възбудимост, предхождащи движението при изследване на реакционно време
    Фонд “Научни изследвания”, № 1407/2004, B-1505/05, 2005-2009.
  9. Електрогенеза на човешки миелинови и демиелинизирани нервни
    влакна: математично моделиране
    № К – 806/98, 1998-2001
  10. Електрогенеза на човешки миелинови и демиелинизирани нервни
    влакна: математично моделиране
    Фонд научни изследвания № 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.

Международно сътрудничество

  • University of Florence, Флоренция, Италия
  • Wright State University, Дейтън, САЩ
  • Medical Center, Бостън, САЩ
  • Institute of Neurology, University College London, Лондон, Великобритания
  • Sport and Exercise Science Research Centre, London South Bank University, Великобритания
  • Medical School of Hannover, Department of Neurology and Clinical Neurophysiology, Хановер, Германия

Награди

  • 2003 – Диана Стефанова – Награда от Министерството на науката и
    образованието на Р България
  • 2006 – Мария Даскалова – Награда за млади учени на Българската академия на науките
Избрани
  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.