The effect of some anesthetics and natural venoms on the LCС-channels functioning of the nuclear membrane of cardiomyocytes and cerebellum Purkinje neurons

Abstract

The investigation of pharmacological sensitivity of the cationic channels in nuclear membrane to the influence of anesthetics and natural venoms is relevant since it was shown that some modulators of N-cholinoreceptors (dithylinum, atracurium) affecting the large conductance cation channels (LCC-channels) functional activity are used in medicine during surgery. In addition, some injectable forms of toxins from the snake venom are used as drugs with an analgesic effect. Therefore, the aim of the study was to investigate the pharmacological sensitivity of the LCC-channels to the muscle relaxants, anaesthetics (mydocalm, diprofol) and natural venoms (neurotoxin II, α-Cobratoxin). The influence of these substances was evaluated based on changes in biophysical parameters of functioning of the LCC-channels of nuclear membrane of the cardiomyocytes and cerebellar Purkinje neurons. Ion currents through these channels were registered in the nucleus-attached or excised patch configuration and the voltage-clamp mode of the patch-clamp technique. We found that mydocalm (2 mM), diprofol (2 mM) and α-Cobratoxin (1 mM) reduced several times the probability of the channels being in the open state. Under the influence of mydocalm and α-Kobratoxin in high concentrations (1-2 mM) the effect of channels flickering was observed which indicates the channel pore blocking in its open state. At the same time, the average amplitude of the K+ current through the LCC-channels decreased by 13 % under the influence of NT II (25 μM). The results will be the basis for identification of new, more effective inhibitors of the LCC-channels that will be promising for the physiological relevance and structure of the channels investigation.