Permissive Modulation of Sphingosine-1-Phosphate-Enhanced Intracellular Calcium on BK Channel of Chromaffin Cells.

Sphingosine-1-phosphate (S1P), is a signaling sphingolipid which acts as a bioactive lipid mediator. We assessed whether S1P had multiplex effects in regulating the large-conductance Ca-activated K channel (BK) in catecholamine-secreting chromaffin cells. Using multiple patch-clamp modes, Ca imaging, and computational modeling, we evaluated the effects of S1P on the Ca-activated K currents () in bovine adrenal chromaffin cells and in a pheochromocytoma cell line (PC12).

Sex-specific I activation in rabbit ventricles with drug-induced QT prolongation.

Background: Female sex is a known risk factor for drug-induced long QT syndrome (diLQTS). We recently demonstrated a sex difference in apamin-sensitive small-conductance Ca-activated K current (I) activation during β-adrenergic stimulation.

Objective: The purpose of this study was to test the hypothesis that there is a sex difference in I in the rabbit models of diLQTS.

Effects of ondansetron on apamin-sensitive small conductance calcium-activated potassium currents in pacing-induced failing rabbit hearts.

Background: Ondansetron, a widely prescribed antiemetic, has been implicated in drug-induced long QT syndrome. Recent patch clamp experiments have shown that ondansetron inhibits the apamin-sensitive small conductance calcium-activated potassium current (I).

Objective: The purpose of this study was to determine whether ondansetron causes action potential duration (APD) prolongation by I inhibition.

Phospholamban regulates nuclear Ca stores and inositol 1,4,5-trisphosphate mediated nuclear Ca cycling in cardiomyocytes.

Aims: Phospholamban (PLB) is the key regulator of the cardiac Ca pump (SERCA2a)-mediated sarcoplasmic reticulum Ca stores. We recently reported that PLB is highly concentrated in the nuclear envelope (NE) from where it can modulate perinuclear Ca handling of the cardiomyocytes (CMs). Since inositol 1,4,5-trisphosphate (IP) receptor (IPR) mediates nuclear Ca release, we examined whether the nuclear pool of PLB regulates IP-induced nuclear Ca handling.

Role of apamin-sensitive small conductance calcium-activated potassium currents in long-term cardiac memory in rabbits.

Background: Apamin-sensitive small conductance calcium-activated K current (I) is up-regulated during ventricular pacing and masks short-term cardiac memory (CM).

Objective: The purpose of this study was to determine the role of I in long-term CM.

Methods: CM was created with 3-5 weeks of ventricular pacing and defined by a flat or inverted T wave off pacing.

Role of Apamin-Sensitive Calcium-Activated Small-Conductance Potassium Currents on the Mechanisms of Ventricular Fibrillation in Pacing-Induced Failing Rabbit Hearts.

Background: Ventricular fibrillation (VF) during heart failure is characterized by stable reentrant spiral waves (rotors). Apamin-sensitive small-conductance calcium-activated potassium currents () are heterogeneously upregulated in failing hearts. We hypothesized that influences the location and stability of rotors during VF.

Phospholamban is concentrated in the nuclear envelope of cardiomyocytes and involved in perinuclear/nuclear calcium handling.

Aims: Phospholamban (PLB) regulates the cardiac Ca-ATPase (SERCA2a) in sarcoplasmic reticulum (SR). However, the localization of PLB at subcellular sites outside the SR and possible contributions to Ca cycling remain unknown. We examined the intracellular distribution of PLB and tested whether a pool of PLB exists in the nuclear envelope (NE) that might regulate perinuclear/nuclear Ca (nCa) handling in cardiomyocytes (CMs).

Antiarrhythmic effects of (-)-epicatechin-3-gallate, a novel sodium channel agonist in cultured neonatal rat ventricular myocytes.

(-)-Epicatechin-3-gallate (ECG), a polyphenol extracted from green tea, has been proposed as an effective compound for improving cardiac contractility. However, the therapeutic potential of ECG on the treatment of arrhythmia remains unknown. We investigated the direct actions of ECG on the modulation of ion currents and cardiac cell excitability in the primary culture of neonatal rat ventricular myocyte (NRVM), which is considered a hypertrophic model for analysis of myocardial arrhythmias.

Lysophospholipids regulate excitability and exocytosis in cultured bovine chromaffin cells.

Bioactive lysophospholipids (LPLs) are released by blood cells and can modulate many cellular activities such as angiogenesis and cell survival. In this study, the effects of sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) on excitability and exocytosis in bovine chromaffin cells were investigated using the whole-cell configuration of the patch-clamp. Voltage-gated Ca(2+) current was inhibited by S1P and LPA pre-treatment in a concentration-dependent manner with IC(50)s of 0.

Identification of two types of ATP-sensitive K+ channels in rat ventricular myocytes.

The ATP-sensitive K(+) (K(ATP)) channels are known to provide a functional linkage between the electrical activity of the cell membrane and metabolism. Two types of inwardly rectifying K(+) channel subunits (i.e.

Changes in membrane cholesterol of pituitary tumor (GH3) cells regulate the activity of large-conductance Ca2+-activated K+ channels.

The effects of changes in membrane cholesterol on ion currents were investigated in pituitary GH3 cells. Depletion of membrane cholesterol by exposing cells to methyl-beta-cyclodextrin (MbetaCD), an oligosaccharide, resulted in an increase in the density of Ca2+-activated K+ current (IK(Ca)). However, no significant change in IK(Ca) density was demonstrated in GH3 cells treated with a mixture of MbetaCD and cholesterol.

Pharmacological roles of the large-conductance calcium-activated potassium channel.

The gating of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel is primarily controlled by intracellular Ca(2+) and/or membrane depolarization. These channels play a role in the coupling of excitation-contraction and stimulus-secretion. A variety of structurally distinct compounds may influence the activity of these channels.

Inhibitory action of L-type Ca2+ current by paeoniflorin, a major constituent of peony root, in NG108-15 neuronal cells.

The effects of paeoniflorin, a glycoside isolated from the root of Paeonia lactiflora, on ion currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG108-15 were investigated. Paeoniflorin (1-300 microM) reversibly produced an inhibition of L-type voltage-dependent Ca2+ current (I(Ca,L)) in a concentration-dependent manner. Paeoniflorin caused no change in the overall shape of the current-voltage relationship of I(Ca,L).