Telezhkin V. Nature of the modulatory effects of NO on the elektrogenesis in and contraction-relaxation of main pulmonary artery smooth muscles

The dissertation is devoted to investigation of the mechanismes of the effects of nitric oxide (NO) on rabbit main pulmonary artery smooth muscle cells (PASMC). In our research, we used nitroglicerine as an NO donor. The first part of the study was carried out on endothelium-denuded multicellular smooth muscle strips, by means of a sucrose-gap technique and tensometry, to measure the smooth muscle electrical and contractile activity and to investigate the modulation action of NO. The second section of the study was carried out on isolated PASMC using a voltage-clamp ("patch-clamp") technique to investigate NO influence on outward transmembrane current, on voltage-gated calcium current, and on currents through single calcium dependent potassium channel of large conductivity (KCa-channel) activity. It has been found that NO relaxes PASMC by means at least of four known mechanismes: stimulates activity of KCa-channel, supresses activity of voltage-gated L-type calcium channels, decreases calcium release from inositoltriphosphate-sensitive calcium stores, and affects contractile apparatus of PASMC. Moreover, in the path-clamp experiments, the outward transmembrane current was activated at potentials more positive than -40 mV, whereas under sucrose-gap conditions (which were quite close to the physiological ones), the potassium chanel activity was observed at the resting membrane potential (which in PASMC is about from -50 to -60 mV). So, such discrepansies suggest that the electrophisiological properties and responses of single PASMC and those of multicellular tussue preparations could significantly differ from each other.