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Ca2+ Exchanger (ca2+ + exchanger)
Selected AbstractsMuscarine activates the sodium,calcium exchanger via M3 receptors in basal forebrain neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2006Changqing Xu Abstract Neurons of the medial septum/diagonal band of Broca (MSDB) project to the hippocampus. Muscarinic cholinergic mechanisms within the MSDB are potent modulators of hippocampal functions; intraseptal scopolamine disrupts and intraseptal carbachol facilitates hippocampus-dependent learning and memory tasks, and the associated hippocampal theta rhythm. In earlier work, we demonstrated that, within the MSDB, the septohippocampal GABAergic but not cholinergic neurons are the primary target of muscarinic manipulations and that muscarinic activation of septohippocampal GABAergic neurons is mediated directly via M3 receptors. In the present study, we examined the ionic mechanism(s) underlying the excitatory actions of muscarine in these neurons. Using whole-cell patch-clamp recording techniques in rat brain slices, we demonstrated that M3 receptor-mediated muscarinic activation of MSDB neurons is dependent on external Na+ and is also reduced by bath-applied Ni2+ and KB-R7943 as well as by replacing external Na+ with Li+, suggesting a primary involvement of the Na+,Ca2+ exchanger. We conclude that the M3 receptor-mediated muscarinic activation of MSDB septohippocampal GABA-type neurons, that is important for cognitive functioning, is mediated via activation of the Na+,Ca2+ exchanger. [source] Remote myocardium gene expression after 30 and 120 min of ischaemia in the ratEXPERIMENTAL PHYSIOLOGY, Issue 2 2006Miguel S. Guerra The aim of the present study was to investigate how early the onset of ischaemia-induced changes in gene expression is in remote myocardium, and whether these changes would be different for left and right ventricles. Wistar rats (n= 27) were randomly assigned to left coronary artery (LCA) ligation for 30 or 120 min and sham groups. Evans Blue infusion revealed antero-apical left ventricle (LV) and left intraventricular (IV) septal ischaemia (35.5 ± 0.6% of LV mass). LCA ligation induced transient LV systolic dysfunction and sustained biventricular slowing of relaxation. Regarding mRNA levels, type B natriuretic peptide (BNP) was upregulated in the LV at 30 (+370 ± 191%) and 120 min (+221 ± 112%), whilst in the right ventricle (RV) this was only significant at 120 min (+128 ± 39%). Hipoxia-inducible factor 1, and interleukin 6 overexpression positively correlated with BNP. Inducible NO synthase upregulation was present in both ventricles at 120 min (LV, +327 ± 195%; RV, +311 ± 122%), but only in the RV at 30 min (+256 ± 88%). Insulin-like growth factor 1 increased in both ventricles at 30 (RV, +59 ± 18%; LV, +567 ± 192%) and 120 min (RV, +69 ± 33%; LV, +120 ± 24%). Prepro-endothelin-1 was upregulated in the RV at 120 min (+77 ± 25%). Ca2+ -handling proteins were selectively changed in the LV at 120 min (sarcoplasmic reticulum Ca2+ ATPase, 53 ± 7%; phospholamban, +31 ± 4%; Na+,Ca2+ exchanger, 31 ± 6%), while Na+,H+ exchanger was altered only in the RV (,79 ± 5%, 30 min; +155 ± 70%, 120 min). Tumour necrosis factor-, and angiotensin converting enzyme were not significantly altered. A very rapid modulation of remote myocardium gene expression takes place during myocardial ischaemia, involving not only the LV but also the RV. These changes are different in the two ventricles and in the same direction as those observed in heart failure. [source] Mechanism of the persistent sodium current activator veratridine-evoked Ca2+ elevation: implication for epilepsyJOURNAL OF NEUROCHEMISTRY, Issue 3 2009Ádám Fekete Abstract Although the role of Na+ in several aspects of Ca2+ regulation has already been shown, the exact mechanism of intracellular Ca2+ concentration ([Ca2+]i) increase resulting from an enhancement in the persistent, non-inactivating Na+ current (INa,P), a decisive factor in certain forms of epilepsy, has yet to be resolved. Persistent Na+ current, evoked by veratridine, induced bursts of action potentials and sustained membrane depolarization with monophasic intracellular Na+ concentration ([Na+]i) and biphasic [Ca2+]i increase in CA1 pyramidal cells in acute hippocampal slices. The Ca2+ response was tetrodotoxin- and extracellular Ca2+ -dependent and ionotropic glutamate receptor-independent. The first phase of [Ca2+]i rise was the net result of Ca2+ influx through voltage-gated Ca2+ channels and mitochondrial Ca2+ sequestration. The robust second phase in addition involved reverse operation of the Na+,Ca2+ exchanger and mitochondrial Ca2+ release. We excluded contribution of the endoplasmic reticulum. These results demonstrate a complex interaction between persistent, non-inactivating Na+ current and [Ca2+]i regulation in CA1 pyramidal cells. The described cellular mechanisms are most likely part of the pathomechanism of certain forms of epilepsy that are associated with INa,P. Describing the magnitude, temporal pattern and sources of Ca2+ increase induced by INa,P may provide novel targets for antiepileptic drug therapy. [source] Changes in extracellular K+ concentration modulate contractility of rat and rabbit cardiac myocytes via the inward rectifier K+ current IK1THE JOURNAL OF PHYSIOLOGY, Issue 3 2004Ron Bouchard The mechanisms underlying the inotropic effect of reductions in [K+]o were studied using recordings of membrane potential, membrane current, cell shortening and [Ca2+]i in single, isolated cardiac myocytes. Three types of mammalian myocytes were chosen, based on differences in the current density and intrinsic voltage dependence of the inwardly rectifying background K+ current IK1 in each cell type. Rabbit ventricular myocytes had a relatively large IK1 with a prominent negative slope conductance whereas rabbit atrial cells expressed much smaller IK1, with little or no negative slope conductance. IK1 in rat ventricle was intermediate in both current density and slope conductance. Action potential duration is relatively short in both rabbit atrial and rat ventricular myocytes, and consequently both cell types spend much of the duty cycle at or near the resting membrane potential. Rapid increases or decreases of [K+]o elicited significantly different inotropic effects in rat and rabbit atrial and ventricular myocytes. Voltage-clamp and current-clamp experiments showed that the effects on cell shortening and [Ca2+]i following changes in [K+]o were primarily the result of the effects of alterations in IK1, which changed resting membrane potential and action potential waveform. This in turn differentially altered the balance of Ca2+ efflux via the sarcolemmal Na+,Ca2+ exchanger, Ca2+ influx via voltage-dependant Ca2+ channels and sarcoplasmic reticulum (SR) Ca2+ release in each cell type. These results support the hypothesis that the inotropic effect of alterations of [K+]o in the heart is due to significant non-linear changes in the current,voltage relation for IK1 and the resulting modulation of the resting membrane potential and action potential waveform. [source] Response properties of isolated mouse olfactory receptor cellsTHE JOURNAL OF PHYSIOLOGY, Issue 1 2001Johannes Reisert 1Response properties of isolated mouse olfactory receptor cells were investigated using the suction pipette technique. Cells were exposed to the odour cineole or to solutions of modified ionic content by rapidly changing the solution superfusing the cilia. All experiments were performed at 37°C. 2Mouse olfactory receptor cells displayed a steep dependence of action potential frequency on stimulus concentration, a 3-fold increase in stimulus concentration often saturating the firing frequency at 200-300 Hz. The receptor current increased more gradually with increasing cineole concentration and did not saturate within the 100-fold range of cineole concentrations applied. 3When stimulated for 30 s with a low odour concentration, cells responded with sporadic spike firing. Higher concentrations led to the generation of a large receptor current at the onset of stimulation which returned to baseline levels within a few seconds, accompanied during its rising phase by a short burst of action potentials. Thereafter an oscillating response pattern was observed during the remainder of the stimulus, consisting of repetitive increases in receptor current of around 1 s duration accompanied by short bursts of action potentials. 4Olfactory adaptation was studied by comparing the responses to two closely spaced odour stimuli. The response to the second odour stimulus recovered to 80% of its original magnitude when the cell was superfused with Ringer solution during the 5 s interval between odour exposures. In contrast, exposure to a choline-substituted low Na+ solution between odour stimuli had two effects. First, the receptor current response to the first odour stimulus did not terminate as quickly as in the presence of Na+, suggesting the presence of a Na+ -Ca2+ exchanger. Second, the response to the second stimulus only recovered to 55% of its original magnitude, demonstrating the involvement of Na+ -Ca2+ exchange in the recovery of sensitivity in mouse olfactory receptor cells following stimulation. [source] | ||||||||||||||||||||||