We hypothesize that the LCC-channels of nuclear membranes are an integral part of intracellular Ca2+ signaling machinery and therefore play an important role in the cell functioning. To test this hypothesis, first necessary thing is to identify an effective and specific blocker of these channels. So far, we have been able to identify only LCC-channel blockers, which act in relatively high concentrations. The structure and physiological role of these channels are unknown, the identification of their specific blocker will be the first step to further understand their physiological role. Identification of an effective and relatively specific channel blocker of a certain type is one of the longest, but also the most important stages for the subsequent study of the physiological role and structure of these channels. The effect of agonists and inhibitors of N (pancuronium, vecuronium and galamine) and M-cholinergic receptors (pilocarpine, acetylcholine, carbacholine, atropine), adrenoreceptors (epinephrine, isoproterenol, propranolol) will be investigated.
Differences in the expression of LCC-channels in different types of cells may be a key clue to understanding their physiological relevance, as our hypothesis suggests the participation of LCC-channels in intracellular Ca2+ signaling. Therefore, the next step is to study the expression of LCC-channels in the nuclear membranes of cells of different types, namely hepatocytes, salivary gland secretory cells, skeletal and smooth muscle cells.
The results obtained with this project will be fundamentally new to science and suitable for being published in journals with a high impact factor. In the future, it is also planned to conduct molecular genetic studies to determine the structure of LCC-channels and to study their role in various pathological conditions. This, in turn, opens a wide field for the development of means of pharmacological correction of these pathological conditions, which is a long-term goal of our work.