Small conductance Ca²⁺-activated K⁺ (SK) and intermediate conductance Ca(2+)-activated K⁺ (IK) channels are thought to be involved in detrusor smooth muscle (DSM) excitability and contractility. Using naphtho[1,2-d]thiazol-2-ylamine (SKA-31), a novel and highly specific SK/IK channel activator, we investigated whether pharmacological activation of SK/IK channels reduced guinea pig DSM excitabil...

RATIONALE Fibrillation/defibrillation episodes in failing ventricles may be followed by action potential duration (APD) shortening and recurrent spontaneous ventricular fibrillation (SVF). OBJECTIVE We hypothesized that activation of apamin-sensitive small-conductance Ca(2+)-activated K(+) (SK) channels is responsible for the postshock APD shortening in failing ventricles. METHODS AND RESUL...

Long lasting outward currents mediated by Ca2+-activated K+ channels can be induced by Ca2+ influx through N-methyl-D-aspartate (NMDA)-receptor channels in voltage-clamped hippocampal pyramidal neurons. Using specific inhibitors, we have attempted to identify the channels that underlie these outward currents. At a holding potential of -50 mV, applications of 1 mM NMDA to the soma of cultured hi...

Nitric oxide (NO) is a radical and a gas, properties that allow NO to diffuse through membranes and potentially enable it to function as a "volume messenger." This study had two goals: first, to investigate the mechanisms by which NO functions as a modulator of neuronal excitability, and second, to compare NO effects produced by NO release from chemical NO donors with those elicited by physiolo...

PURPOSE Effects of haloperidol on K(+) currents (IKs) of rat retinal ganglion cells (RGCs) were examined, with the hypothesis that its alteration of IKs explains alterations in the pattern electroretinogram (PERG). METHODS Fast blue was injected into superior colliculi of rats (3-8 days old) to identify RGCs under epifluorescence illumination after retrograde transport to retinas. Retinas wer...

Hyperinsulinemia is a risk factor for hypertension and arteriosclerosis. The mechanism by which it contributes to disease progression is not known. The present study examines the effects of insulin on endothelium-derived relaxing factors. Segments of rat mesenteric arterioles and aorta were set up for isometric recordings. The effect of insulin (1 mU/mL) on acetylcholine responses was examined ...

The vasodilator response to bradykinin (BK) appears to be mediated by a number of different endothelium-derived relaxing factors (EDRFs). The EDRFs mediating the response depend on the species and vascular bed studied. The mechanism by which BK dilates the hindlimb vascular bed was investigated in the anesthetized rat. BK produced dose-dependent increases hindlimb blood flow. The NOS antagonist...

The synthesis and pharmacological testing of two series of novel bis-quinolinium cyclophanes as blockers of the apamin-sensitive Ca(2+)-activated K(+) (SK(Ca)) channel are presented. In these cyclophanes the two 4-aminoquinolinium groups are joined at the ring N atoms (linker L) and at the exocyclic N atoms (linker A). In those cases where A and L contain two or more aromatic rings each, the ac...

OBJECTIVE Protease-activated receptors (PARs) 1 and 2 are expressed in various blood vessels including rat aorta, modulating vascular tone. We investigated the roles of PAR-1 and PAR-2 in vasomotor modulation in rat superior mesenteric artery. METHODS AND RESULTS Effects of the PAR-2-activating peptide Ser-Leu-Ile-Gly-Arg-Leu-amide (SLIGRL-amide) and the PAR-1-activating peptide Thr-Phe-Leu-L...

L-serine is a precursor of central neurotransmitters. Its cardiovascular effects are largely unstudied. We compared the in vitro effects of L-serine and acetylcholine in phenylephrine-constricted third-order branches of mesenteric arterioles in the NO synthase inhibitor N(G)-nitro L-arginine methyl ester (L-NAME), pretreated hypertensive rats, and a control group of normotensive male Sprague-Da...