Inwardly rectifying potassium (Kir) channels play key roles in functions, including maintaining the resting membrane potential and regulating the action potential duration in excitable cells. Using in situ whole-cell recordings, we investigated Kir currents in mouse fungiform taste bud cells (TBCs) and immunologically identified the cell types (type I-III) expressing these currents. We demonstrated that Kir currents occur in a cell-type-independent manner. The activation potentials we measured were -80 to -90 mV, and the magnitude of the currents increased as the membrane potentials decreased, irrespective of the cell types. The maximum current densities at -120 mV showed no significant differences among cell types (p>0.05, one-way ANOVA). The density of Kir currents was not correlated with the density of either transient inward currents or outwardly rectifying currents, although there was significant correlation between transient inward and outwardly rectifying current densities (p<0.05, test for no correlation). RT-PCR studies employing total RNA extracted from peeled lingual epithelia detected mRNAs for Kir1, Kir2, Kir4, Kir6, and Kir7 families. These findings indicate that TBCs express several types of Kir channels functionally, which may contribute to regulation of the resting membrane potential and signal transduction of taste.
The model for studying the mechanism of G protein-mediated signalling cannot account for the observation that high-affinity binding of agonists to many different receptors is not dissociated by the addition of high concentrations of guanine nucleotides. Using the cerebral Ai-adenosine receptor as a model system, we have recently identified a component which is responsible for this phenomenon. This protein, termed the coupling cofactor, can be solubilized from brain membranes and chromatographically resolved from both the G proteins and the receptor. Following reconstitution into appropriate acceptor membranes, the coupling cofactor confers resistance of high-affinity agonist binding to guanine nucleotides. The coupling cofactor acts as a brake and limits receptor-dependent signal amplification; in addition, it is a candidate for participating in the higher level organization of receptors and G proteins in membranes and in the membrane-delimited cross-talk between individual receptors. Here, we present a working hypothesis on the possible biological roles of the coupling cofactor.
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
Vision is a fascinating example of the interaction of a biological system with the outside world. The first step of translating electromagnetic energy into a biologically recognizable signal involves the phototransduction cascade in retinal photoreceptor cells. Phototransduction is the best studied example of a GTP binding protein (G protein)- coupled signal transduction pathway. A great body of knowledge about phototransduction has been established in the past several decades but there are still many unanswered questions, particularly about photoresponse recovery and adaptation. The purpose of this review is to outline the events following photon absorption by vertebrate photoreceptors, to demonstrate the great complexity of the phototransduction cascade mechanisms, and to point out some of the controversies arising from recent fmdings in the field of visual transduction.