The acidic tumor microenvironment (TME) of pancreatic cancer affects the physiological function of pancreatic stellate cells (PSCs), which in turn promotes cancer progression. Acid-sensing ion channel 1a (ASIC1a) is responsible for acidosis-related physiopathological processes. In this study, we investigated the effect of acid exposure on the activation and autophagy of PSCs, and the role of ASIC1a in these events. The results showed that acidic medium upregulated the expression of ASIC1a, induced PSCs activation and autophagy, which can be suppressed by inhibiting ASIC1a using PcTx1 or ASIC1a knockdown, suggesting that ASIC1a involves these two processes. In addition, the acidinduced activation of PSCs was impaired after the application of autophagy inhibitor alone or in combination with ASIC1a siRNA, meaning a connection between autophagy and activation. Collectively, our study provides evidence for the involvement of ASIC1a in the acid-caused PSCs activation, which may be associated with autophagy induction.
Peroperative epicardial mapping of activation, recovery and activation-recovery intervals in the human heart has been performed in a group of 12 patients. These patients had the coronary disease but electrocardiograms with normal characteristics. For this mapping, 240 unipolar electrograms were simultaneously recorded with the system SATAPEC built in our laboratory. The results confirm the classical data obtained on the dog heart. In particular, it was well established that the duration of activation corresponding to activation-recovery intervals is shorter at the base than at the apex of the posterior surface of the heart. With SATAPEC it is very easy to obtain epicardial mapping of electrical activity in a few minutes during open heart surgery.
Patch clamp method developed more than 30 years ago is widely used for investigation of cellular excitability manifested as transmembrane ionic current and/or generation of action potentials. This technique could be applied to measurement of ionic currents flowing through individual (single) ion channels or through the whole assembly of ion channels expressed in the whole cell. Whole cell configuration is more common for measurement of ion currents and the only one enabling measurement of action potentials. This method allows detailed analysis of mechanisms and structural determinants of voltagedependent gating of ion channels as well as regulation of channel activity by intracellular signaling pathways and pharmacological agents., M. Karmažínová, L'. Lacinová., and Obsahuje bibliografii a bibliografické odkazy