1. Dear Colleagues!

I am glad to see you, and I pleased to present you few words about

pharmacogenetic aspects f channelopaties. Pharmacogenetic study inherited characteristics of metabolism, .

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An action potential is a first event, which leads to a contraction of cardiomyocytes or transmission of nerve impulses .

An action potential is a short event in which the electrical membrane potential of a cell rapidly rises and falls, following a stereotyped trajectory. Action potentials occur in several types of cells, called excitable cells. In neurous cells they play a central role in cell-to-cell communication. In other types of cells, their main function is to activate intracellular processes. In muscle cells, an AP is the first step in the chain of events leading to contraction.

AP is generated by special types of voltage-gated ion channels embedded in a cell's plasma membrane and carried out by depolarization and ion currents. is carried out by in-ward currents of sodium (Na +) 2 + , nd is carried out by out-ward currents of potassium (K +) from the cells.

Special characteristic of AP, in comparison with neuronal AP is a phase 2-plato, which is mainly carried out by in-ward currents of 2 +, considerably prolonging AP (about 200-300 ).

3. Inherited disturbance of channels structure or acquired disturbances of their

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functions lead to prolonged AP, that may clinical be expressed by developing cardiac arrhythmia. Taking drugs is one of the main external factors, which lead to a cardiac arrhythmia. There are few several types of cardiac arrhythmia may developed, but the most important for us is QT-int.prolongation and PVT. Because QT-int length depend on heart rate, it is necessary to calculated QT corrected. Usually it is calculated by Bazets formula, but also we can do it using QT-int nomogram. LQTS may by primary or secondary. Primary LQTS due to significant genetic modification of ion channels/ .

8. There are soft mutations which appears clinical only in case of the external provocation. There isnt a clear difference between the primary and secondary LQTS as between the mutation and polymorphism. .9. 10/ Inherited ch/p are caused by gene mutations, coding different subunits of ion channels and influence on changes duration respective parts of AP. 11/ 12. In patients with TdP clinically we can see 14. Each individuals have a physiological cardiac repolarisation reserve. This functional reserve allows to counterbalance any endogenous (genetic defects or cardiac disorders for instance) or exogenous (drugs for example) factors that would either reduce repolarising or increase depolarising currents during the AP. The extent of this cardiac repolarisation reserve is variable, and may be reduced in some individuals. Individuals with a reduced repolarisation reserve are more susceptible to developing significant and manifest LQT and TdP when exposed to IKr blocking drugs. Women tend to have a longer QT interval, most probably because their cardiac cells generate less repolarising current. The reduced repolarisation reserve in women may explain their increased propensity to develop TdP when taking QT interval prolonging drugs. The magnitude of repolarisation reserve is genetically determined. Asymptomatic individuals with normal or borderline ECGs at baseline, may harbour genetic variants reducing their cardiac repolarising currents, corresponding to a forme fruste of LQTS and manifest QT interval prolongation when taking an IKr blocking drugs. 16. I want to show you an animation from Dr.Witchel from a website // Just you minits, Now, Dr.Witchel tell about inactivating of potassium