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ca2+ + exchange)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Cellular Physiology of Retinal and Choroidal Arteriolar Smooth Muscle Cells

MICROCIRCULATION, Issue 1 2007
C. N. SCHOLFIELD
ABSTRACT Control of ocular blood flow occurs predominantly at the level of the retinal and choroidal arterioles. The present article provides an overview of the Ca2 + handling mechanisms and plasmalemmal ion channels involved in the regulation of retinal and choroidal arteriolar smooth muscle tone. Increases in global intracellular free Ca2 + ([Ca2 +]i) involve multiple mechanisms, including agonist-dependent release of Ca2 + from intracellular stores through activation of the inositol trisphosphate (IP3) pathway. Ca2 + enters by voltage-dependent L-type Ca2 + channels and novel dihydropyridine-sensitive store-operated nonselective cation channels. Ca2 + extrusion is mediated by plasmalemmal Ca2 + -ATPases and through Na+/Ca2+ exchange. Local Ca2 + transients (Ca2 + sparks) play an important excitatory role, acting as the building blocks for more global Ca2 + signals that can initiate vasoconstriction. K+ and Cl, channels may also affect cell function by modulating membrane potential. The precise contribution of each of these mechanisms to the regulation of retinal and choroidal perfusion in vivo warrants future investigation. [source]

Decreased activity of the smooth muscle Na+/Ca2+ exchanger impairs arteriolar myogenic reactivity

THE JOURNAL OF PHYSIOLOGY, Issue 6 2008
Hema Raina
Arteriolar myogenic vasoconstriction occurs when stretch or increased membrane tension leads to smooth muscle cell (SMC) depolarization and opening of voltage-gated Ca2+ channels. While the mechanism underlying the depolarization is uncertain a role for non-selective cation channels has been demonstrated. As such channels may be expected to pass Na+, we hypothesized that reverse mode Na+/Ca2+ exchange (NCX) may act to remove Na+ and in addition play a role in myogenic signalling through coupled Ca2+ entry. Further, reverse (Ca2+ entry) mode function of the NCX is favoured by the membrane potential found in myogenically active arterioles. All experiments were performed on isolated rat cremaster muscle first order arterioles (passive diameter ,150 ,m) which were pressurized in the absence of intraluminal flow. Reduction of extracellular Na+ to promote reverse-mode NCX activity caused significant, concentration-dependent vasoconstriction and increased intracellular Ca2+. This vasoconstriction was attenuated by the NCX inhibitors KB-R7943 and SEA 04000. Western blotting confirmed the existence of NCX protein while real-time PCR studies demonstrated that the major isoform expressed in the arteriolar wall was NCX1. Oligonucleotide knockdown (24 and 36 h) of NCX inhibited the vasoconstrictor response to reduced extracellular Na+ while also impairing both steady-state myogenic responses (as shown by pressure,diameter relationships) and acute reactivity to a 50 to 120 mmHg pressure step. The data are consistent with reverse mode activity of the NCX in arterioles and a contribution of this exchanger to myogenic vasoconstriction. [source]

Electrophysiological properties of two axonal sodium channels, Nav1.2 and Nav1.6, expressed in mouse spinal sensory neurones

THE JOURNAL OF PHYSIOLOGY, Issue 3 2005
Anthony M. Rush
Sodium channels Nav1.2 and Nav1.6 are both normally expressed along premyelinated and myelinated axons at different stages of maturation and are also expressed in a subset of demyelinated axons, where coexpression of Nav1.6 together with the Na+/Ca2+ exchanger is associated with axonal injury. It has been difficult to distinguish the currents produced by Nav1.2 and Nav1.6 in native neurones, and previous studies have not compared these channels within neuronal expression systems. In this study, we have characterized and directly compared Nav1.2 and Nav1.6 in a mammalian neuronal cell background and demonstrate differences in their properties that may affect neuronal behaviour. The Nav1.2 channel displays more depolarized activation and availability properties that may permit conduction of action potentials, even with depolarization. However, Nav1.2 channels show a greater accumulation of inactivation at higher frequencies of stimulation (20,100 Hz) than Nav1.6 and thus are likely to generate lower frequencies of firing. Nav1.6 channels produce a larger persistent current that may play a role in triggering reverse Na+/Ca2+ exchange, which can injure demyelinated axons where Nav1.6 and the Na+/Ca2+ exchanger are colocalized, while selective expression of Nav1.2 may support action potential electrogenesis, at least at lower frequencies, while producing a smaller persistent current. [source]

NANOMOLAR LEVEL OF OUABAIN INCREASES INTRACELLULAR CALCIUM TO PRODUCE NITRIC OXIDE IN RAT AORTIC ENDOTHELIAL CELLS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2004
Xian Hui Dong
Summary 1.,Changes in [Ca2+]i across the cell membrane and/or the sarcoplasmic reticulum regulate endothelial nitric oxide (NO) synthase activity. 2.,In the present study, we investigated the effect of ouabain, a specific inhibitor of Na+/K+ -ATPase, on NO release and [Ca2+]i movements in cultured rat aortic endothelial cells (RAEC) by monitoring NO production continuously using an NO-specific real-time sensor and by measuring the change in [Ca2+]i using a fluorescence microscopic imaging technique with high-speed wavelength switching. The t½ (half-time of the decline of [Ca2+]i to basal levels after stimulation with 10 µmol/L bradykinin) was used as an index of [Ca2+]i extrusion. 3.,A very low concentration of ouabain (10 nmol/L) did not increase the peak of NO production, but decreased the decay of NO release and, accordingly, increased integral NO production by the maximal dose,response concentration induced by bradykinin. The same dose of ouabain affected [Ca2+]i movements across the cell membrane and/or sarcoplasmic reticulum induced by bradykinin with a time-course similar to that of NO release. Moreover, the t½ was significantly increased. 4.,Pretreatment of RAEC with Na+ -free solution, an inhibitor of the Na+/Ca2+ exchanger, and nickel chloride hexahydrate prevented the effects induced by bradykinin and ouabain. 5.,These observations using real-time recording indicate that a small amount of ouabain contributes to the bradykinin-stimulated increase of NO production through inhibition of plasma membrane Na+/K+ -ATPase activity and an increase in intracellular Na+ concentrations. The membrane was then depolarized, leading to a decline in the bradykinin-stimulated increase in [Ca2+]i by forward mode Na+/Ca2+ exchange to prolong the Ca2+ signal time. 6.,From these results, we suggest that nanomolar levels of ouabain modulate [Ca2+]i movements and NO production in RAEC. [source]