Search results for "CHANNELS"
showing 10 items of 411 documents
Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2.
2003
Headache attacks and autonomic dysfunctions characterize migraine, a very common, disabling disorder with a prevalence of 12% in the general population of Western countries(1,2). About 20% of individuals affected with migraine experience aura, a visual or sensory-motor neurological dysfunction that usually precedes or accompanies the headache(3). Although the mode of transmission is controversial(4), population-based and twin studies have implicated genetic factors, especially in migraine with aura(5,6). Familial hemiplegic migraine is a hereditary form of migraine characterized by aura and some hemiparesis. Here we show that mutations in the gene ATP1A2 that encodes the alpha2 subunit of t…
Role of K+ and Ca2+ fluxes in the cerebroarterial vasoactive effects of sildenafil
2007
The aim of this study was to assess the role of K(+) and Ca(2+) fluxes in the cerebroarterial vasoactive effects of the phosphodiesterase-5 inhibitor sildenafil. We used isolated rabbit basilar arteries to assess the effects of extracellular K(+) raising on sildenafil-induced vasodilatation, and studied the pharmacological interaction of sildenafil with selective modulators of membrane K(+) and Ca(2+) channels. Expression of Kv1 subunits of K(+) channels was assessed at messenger and protein levels. Parallel experiments were carried out with zaprinast for comparison. Sildenafil (10 nM-0.1 mM) induced concentration-dependent relaxation of endothelin-1 (10 nM)-precontracted arteries, which wa…
Characterization of two different Ca2+ entry pathways dependent on depletion of internal Ca2+ pools in rat aorta
1998
Ryanodine (10 microM), thapsigargin (1 microM) and cyclopiazonic acid (10 microM) produced a slow, sustained contractile response in rat aorta that only can be observed in Ca2+-containing solution. In Ca2+-free medium, no response to the drugs was obtained, which suggests that the contraction elicited in presence of Ca2+ is mainly due to the contribution of extracellular influx. This Ca2+ entry does not depend on the opening of dihydropyridine-dependent Ca2+-channels for nimodipine does not affect this. Noradrenaline (1 microM) induced a biphasic response in Ca2+-free medium that was mediated by two different Ca2+ compartments, one of which is common to caffeine (10 mM), and is also deplete…
Inhibition by Fendiline of the Transient Outward Current in Rat Ventricular Cardiomyocytes
1999
The effects of fendiline on the transient outward current (Ito) were investigated in rat ventricular cardiomyocytes. Extracellularly applied fendiline reduced peak and steady-state current amplitude of Ito; the inactivation of Ito was accelerated by the drug, which reflects onset of block. The described effects were concentration dependent: half-maximal effects were achieved at approximately 3 microM fendiline. Intracellularly applied fendiline (3 microM) did not affect Ito within 5 min. The steady-state current amplitude of Ito was more efficiently suppressed by the drug at 22 +/- 1 degrees C than at 36 +/- 1 degrees C. The recovery of Ito was analyzed by the application of twin depolarizi…
Mechanism of Block by 4-Aminopyridine of the Transient Outward Current in Rat Ventricular Cardiomyocytes
1998
The effects of 4-aminopyridine (4-AP) on the transient outward current (I to ) were investigated in rat ventricular cardiomyocytes at different values of intracellular pH (pH i ) and extracellular pH (pH o ). The 4-AP was administered either extracellularly (bath application) or intracellularly (diffusion from the intrapipette solution). The 4-AP diminished I to given either from inside or outside the cell membrane. The block by extracellularly applied 4-AP (4-AP o ) of the peak amplitude of I to was decreased by external acidification but increased by external alkalinization: conversely. the block by 4-AP o was decreased by internal alkalinization but increased by internal acidification. I…
Expression of Na+-d-glucose cotransporter SGLT2 in rodents is kidney-specific and exhibits sex and species differences
2012
With a novel antibody against the rat Na+-d-glucose cotransporter SGLT2 (rSGLT2-Ab), which does not cross-react with rSGLT1 or rSGLT3, the ∼75-kDa rSGLT2 protein was localized to the brush-border membrane (BBM) of the renal proximal tubule S1 and S2 segments (S1 > S2) with female-dominant expression in adult rats, whereas rSglt2 mRNA expression was similar in both sexes. Castration of adult males increased the abundance of rSGLT2 protein; this increase was further enhanced by estradiol and prevented by testosterone treatment. In the renal BBM vesicles, the rSGLT1-independent uptake of [14C]-α-methyl-d-glucopyranoside was similar in females and males, suggesting functional contribution of…
Diabetes impairs the atrial natriuretic peptide relaxant action mediated by potassium channels and prostacyclin in the rabbit renal artery.
2012
Diabetes is associated with increased prevalence of hypertension, cardiovascular and renal disease. Atrial natriuretic peptide (ANP) plays an important role in cardiovascular pathophysiology and is claimed to have cardioprotective and renoprotective effect in diabetic patients. The working hypothesis was that alloxan-induced diabetes might modify the vascular effects of ANP in isolated rabbit renal arteries and the mechanisms involved in such actions. Plasma ANP levels were higher in diabetic rabbits than in control rabbits. ANP (10(-12)-10(-7)M) induced a relaxation of precontracted renal arteries, which was lower in diabetic than in control rabbits. In arteries from both groups of animals…
4-Aminopyridine and barium chloride attenuate the anti-epileptic effect of carbamazepine in hippocampal slices
1991
The exact mode of action of the anti-epileptic agent carbamazepine is unknown. In hippocampal slices in which epileptiform discharges were induced by addition of penicillin to the perfusion medium, the depressant effect of carbamazepine was attenuated by the potassium-channel blockers barium chloride (0.1 mM) and 4-aminopyridine (200 microM), which suggested that potassium fluxes might be involved in the mechanism of action of carbamazepine.
Acute relaxant effects of 17-beta-estradiol through non-genomic mechanisms in rabbit carotid artery.
2002
Estrogens could play a cardiovascular protective role not only by means of systemic effects but also by means of direct effects on vascular structure and function. We have studied the acute effects and mechanisms of action of 17-beta-estradiol on vascular tone of rabbit isolated carotid artery. 17-Beta-estradiol (10, 30, and 100 microM) elicited concentration-dependent relaxation of 50 mM KCl-induced active tone in male and female rabbit carotid artery. The stereoisomer 17-alpha-estradiol showed lesser relaxant effects in male rabbits. Endothelium removal did not modify relaxation induced by 17-beta-estradiol. The NO synthase inhibitor L-NAME (100 microM) only reduced significantly relaxati…
Functional evidence for different roles of GABAA and GABAB receptors in modulating mouse gastric tone
2010
Abstract The aims of the present study were to investigate, using mouse whole stomach in vitro , the effects of γ-aminobutyric acid (GABA) and GABA receptor agonists on the spontaneous gastric tone, to examine the subtypes of GABA receptors involved in the responses and to determine the possible site(s) of action. GABA induced gastric relaxation, which was antagonized by the GABA A -receptor antagonist, bicuculline, potentiated by phaclofen, GABA B -receptor antagonist, but not affected by 1,2,5,6-Tetrahydropyridin-4-yl methylphosphinic acid hydrate (TPMPA), GABA C -receptor antagonist. Muscimol, GABA A -receptor agonist, mimicked GABA effects inducing relaxation, which was significantly re…