Characterization of L-type calcium channel activity in atrioventricular nodal myocytes from rats with streptozotocin-induced Diabetes mellitus.

Cardiovascular complications are common in patients with Diabetes mellitus (DM). In addition to changes in cardiac muscle inotropy, electrical abnormalities are also commonly observed in these patients. We have previously shown that spontaneous cellular electrical activity is altered in atrioventricular nodal (AVN) myocytes, isolated from the streptozotocin (STZ) rat model of type-1 DM.

Background synaptic activity in rat entorhinal cortex shows a progressively greater dominance of inhibition over excitation from deep to superficial layers.

The entorhinal cortex (EC) controls hippocampal input and output, playing major roles in memory and spatial navigation. Different layers of the EC subserve different functions and a number of studies have compared properties of neurones across layers. We have studied synaptic inhibition and excitation in EC neurones, and we have previously compared spontaneous synaptic release of glutamate and GABA using patch clamp recordings of synaptic currents in principal neurones of layers II (L2) and V (L5).

Smooth muscle Ca(2+) -activated and voltage-gated K+ channels modulate conducted dilation in rat isolated small mesenteric arteries.

Objective:   To assess the influence of blocking smooth muscle large conductance Ca(2+) -activated K+ channels and voltage-gated K+ channels on the conducted dilation to ACh and isoproterenol.

Materials And Methods:   Rat mesenteric arteries were isolated with a bifurcation, triple-cannulated, pressurized and imaged using confocal microscopy. Phenylephrine was added to the superfusate to generate tone, and agonists perfused into a sidebranch to evoke local dilation and subsequent conducted dilation into the feed artery.

A novel role for HNO in local and spreading vasodilatation in rat mesenteric resistance arteries.

Nitric oxide-mediated vasodilatation has previously been attributed to the uncharged form of the molecule (NO(•)), but increasing evidence suggests that nitroxyl (HNO) may play a significant role in endothelium-dependent relaxation. The aim of this study was to investigate the mechanisms underlying HNO-mediated vasodilatation in phenylephrine pre-constricted pressurized (70 mmHg) mesenteric arteries, and on membrane currents in isolated smooth muscle cells using whole cell and perforated patch clamp recordings. Angeli's salt (AS: nitroxyl donor), evoked concentration-dependent vasodilatation that was insensitive to the NO(•) scavengers carboxy-PTIO and hydroxocobalamin (HXC), but sensitive to either the HNO scavenger L-cysteine, K-channel blockers (4-AP and iberiotoxin), raised [K(+)](o), or inhibition of soluble guanylyl cyclase (ODQ).

Streptozotocin-induced diabetes modulates action potentials and ion channel currents from the rat atrioventricular node.

The present study was conducted to evaluate whether experimentally induced type 1 diabetes results in alterations to atrioventricular nodal (AVN) electrophysiology at the cellular level. Spontaneous action potentials (APs) and ionic currents were recorded from AVN myocytes isolated from the hearts of control rats and from those with streptozotocin-induced diabetes. Perforated patch-clamp recordings were used to assess changes in cellular AP parameters and in ionic currents.

Nitric oxide suppresses cerebral vasomotion by sGC-independent effects on ryanodine receptors and voltage-gated calcium channels.

Background/aims: In cerebral arteries, nitric oxide (NO) release plays a key role in suppressing vasomotion. Our aim was to establish the pathways affected by NO in rat middle cerebral arteries.

Methods: In isolated segments of artery, isometric tension and simultaneous measurements of either smooth muscle membrane potential or intracellular [Ca(2+)] ([Ca(2+)](SMC)) changes were recorded.

Endothelium-dependent vasodilation in myogenically active mouse skeletal muscle arterioles: role of EDH and K(+) channels.

As smooth muscle cell (SMC) membrane potential (E(m)) is critical for vascular responsiveness, and arteriolar SMCs are depolarized at physiological intraluminal pressures, we hypothesized that myogenic tone impacts on dilation mediated by endothelium-derived hyperpolarization (EDH). Studies were performed on cannulated mouse cremaster arterioles [diameter, 33+/-2 microm (n=23) at 60 mmHg; SMC Em -34.6+/-1.

Cellular localization of mitochondria contributes to Kv channel-mediated regulation of cellular excitability in pulmonary but not mesenteric circulation.

Mitochondria are proposed to be a major oxygen sensor in hypoxic pulmonary vasoconstriction (HPV), a unique response of the pulmonary circulation to low oxygen tension. Mitochondrial factors including reactive oxygen species, cytochrome c, ATP, and magnesium are potent modulators of voltage-gated K(+) (K(v)) channels in the plasmalemmal membrane of pulmonary arterial (PA) smooth muscle cells (PASMCs). Mitochondria have also been found close to the plasmalemmal membrane in rabbit main PA smooth muscle sections.

Mitochondria-dependent regulation of Kv currents in rat pulmonary artery smooth muscle cells.

Voltage-gated K(+) (Kv) channels are important in the regulation of pulmonary vascular function having both physiological and pathophysiological implications. The pulmonary vasculature is essential for reoxygenation of the blood, supplying oxygen for cellular respiration. Mitochondria have been proposed as the major oxygen-sensing organelles in the pulmonary vasculature.

Potent inhibition of human cardiac potassium (HERG) channels by the anti-estrogen agent clomiphene-without QT interval prolongation.

The acquired form of the long-QT syndrome (LQTS) is a major safety consideration for the development and subsequent use of both cardiac and non-cardiac drugs; it is usually associated with pharmacological inhibition of cardiac HERG-encoded potassium channels. Clomiphene is an anti-estrogen agent used extensively in the treatment of infertility and is not associated with a risk of QT interval prolongation, in contrast to a structurally related compound tamoxifen. We describe here a potent inhibitory effect (IC(50) = 0.

Characteristics of single cells isolated from the atrioventricular node of the adult guinea-pig heart.

To date, data regarding the cellular electrophysiology of the atrioventricular node (AVN) have derived from AVN cells isolated from the rabbit heart. The aim of this study was to characterise for the first time the electrophysiological properties of single cells isolated from the AVN of the guinea-pig heart. Cells were isolated from the AVN region by a combination of enzymatic and mechanical dispersion.

Inhibitory effects of the antiestrogen agent clomiphene on cardiac sarcolemmal anionic and cationic currents.

The aim of this study was to determine the effects of the antiestrogen agent clomiphene on cardiac anionic and cationic sarcolemmal ion channels. Whole-cell recordings were made from rat and guinea pig ventricular myocytes. Clomiphene inhibited the volume-regulated chloride current [I(Cl,vol), activated by cell swelling after hypotonic shock (approximately 145 mOsM)] with an IC(50) value of approximately 9.