Hypotonic solution alters ion channel activity, but little attention has been paid to voltage-dependent sodium channels. The aim of this study was to investigate the effects of hypotonic solution on transient sodium currents (INaT) and persistent sodium currents (INaP). We also explored whether the intracellular signal transduction systems participated in the hypotonic modifications of sodium currents. INaT and INaP were recorded by means of whole-cell patch-clamp technique in isolated rat ventricular myocytes. Our results revealed that hypotonic solution reduced INaT and simultaneously augmented INaP with the occurrence of interconversion between INaT and INaP. Hypotonic solution shifted steady-state inactivation to a more negative potential, prolonged the time of recovery from inactivation, and enhanced intermediate inactivation (IIM). Ruthenium red (RR, inhibitor of TRPV4), bisindolylmaleimide VI (BIM, inhibitor of PKC), Kn-93 (inhibitor of Ca/CaMKII) and BAPTA (Ca2+-chelator) inhibited the effects of hypotonic solution on INaT and INaP. Therefore we conclude that hypotonic solution inhibits INaT, enhances INaP and IIM with the effects being reversible. TRPV4 and intracellular Ca2+, PKC and Ca/CaMKII participate in the hypotonic modifications of sodium currents., L. Hu ... [et al.]., and Obsahuje seznam literatury
Depression is a complex disorder related to chronic inflammatory processes, chronic stress changes and a hippocampal response. There is a increasing knowledge about the role of glial cells in nutrient supply to neurons, maintenance of synaptic contacts and tissue homeostasis within the CNS. Glial cells, viewed in the past as passive elements with a limited influence on neuronal function, are becoming recognized as active partners of neurons and are starting to be discussed as a possible therapeutic target. Their role in the pathogenesis of depressive disorders is also being reconsidered. Attention is devoted to studies of the different types of antidepressants and their effects on transmembrane signaling, including levels of α subunits of G proteins in C6 glioma cells in vitro as a model of postsynaptic changes in vivo. These models indicate similarities in antidepressant effects on G proteins of brain cells and effector cells of natural immunity, natural killers and granulocytes. Thus, an antidepressant response can exhibit certain common characteristics in functionally different systems which also participate in disease pathogenesis. There are, however, differences in the astrocyte G-protein responses to antidepressant treatment, indicating that antidepressants differ in their effect on glial signalization. Today mainstream approach to neurobiological basis of depressive disorders and other mood illnesses is linked to abnormalities in transmembrane signal transduction via G-protein coupled receptors. Intracellular signalization cascade modulation results in the activation of transcription factors with subsequent increased production of a wide array of products including growth factors and to changes in cellular activity and reactivity., M. Páv, H. Kovářů, A. Fišerová, E. Havrdová, V. Lisá., and Obsahuje bibliografii a bibliografické odkazy