Osmotic modulation of slowly activating IKs in guinea-pig ventricular myocytes.

Aims: The aims of the study were to determine the effects of anisosmotic bathing solution on selected properties of I(Ks), the slowly activating delayed-rectifier K(+) current important for repolarization of the action potential in cardiac cells.

Methods And Results: Guinea-pig ventricular myocytes were voltage-clamped using either the ruptured-patch or perforated-patch technique, and the amplitude, time course, and voltage dependence of I(Ks) were determined before [isosmotic (1T)] and during superfusion of hyposmotic (<1T) or hyperosmotic (>1T) bathing solution. Hyposmotic solution increased the amplitude of I(Ks), and hyperosmotic solution decreased it.

Electroporation-induced inward current in voltage-clamped guinea pig ventricular myocytes.

Electroporation induced by high-strength electrical fields has long been used to investigate membrane properties and facilitate transmembrane delivery of molecules and genes for research and clinical purposes. In the heart, electric field-induced passage of ions through electropores is a factor in defibrillation and postshock dysfunction. Voltage-clamp pulses can also induce electroporation, as exemplified by findings in earlier studies on rabbit ventricular myocytes: Long hyperpolarizations to ≤-110 mV induced influx of marker ethidium and irregular inward currents that were as large with external NMDG(+) as Na(+).

Regulation of wild-type and mutant KCNQ1/KCNE1 channels by tyrosine kinase.

The objective of the study was to investigate the role of tyrosine phosphorylation in the regulation of KCNQ1/KCNE1 channels. Large whole-cell time- and voltage-dependent K(+) currents were present in human embryonic kidney 293 cells cotransfected with human KCNQ1 and KCNE1 but not in control nontransfected cells. The time- and voltage-dependent current had biophysical properties typical of cardiac KCNQ1/KCNE1 current and was almost completely abolished by KCNQ1 blocker chromanol 293B (50 microM).

Involvement of tyrosine kinase in the hyposmotic stimulation of I Ks in guinea-pig ventricular myocytes.

The objective of this study was to investigate the involvement of tyrosine phosphorylation in the hyposmotic stimulation of cardiac I Ks, a slowly activating delayed-rectifier K+ current that promotes repolarization of the action potential. The current was recorded from whole-cell-configured guinea-pig ventricular myocytes before, during, and after their exposure to solution whose osmolarity was 0.75 times normal.

Role of kinases and G-proteins in the hyposmotic stimulation of cardiac IKs.

Exposure of cardiac myocytes to hyposmotic solution stimulates slowly-activating delayed-rectifying K(+) current (I(Ks)) via unknown mechanisms. In the present study, I(Ks) was measured in guinea-pig ventricular myocytes that were pretreated with modulators of cell signaling processes, and then exposed to hyposmotic solution. Pretreatment with compounds that (i) inhibit serine/threonine kinase activity (10-100 microM H89; 200 microM H8; 50 microM H7; 1 microM bisindolylmaleimide I; 10 microM LY294002; 50 microM PD98059), (ii) stimulate serine/threonine kinase activity (1-5 microM forskolin; 0.

Insensitivity of cardiac delayed-rectifier I(Kr) to tyrosine phosphorylation inhibitors and stimulators.

1. The rapidly activating delayed-rectifying K+ current (I(Kr)) in heart cells is an important determinant of repolarisation, and decreases in its density are implicated in acquired and inherited long QT syndromes. The objective of the present study on I(Kr) in guinea-pig ventricular myocytes was to evaluate whether the current is acutely regulated by tyrosine phosphorylation.

Tyrosine kinase and phosphatase regulation of slow delayed-rectifier K+ current in guinea-pig ventricular myocytes.

The objective of this study was to investigate the involvement of tyrosine phosphorylation in the regulation of the cardiac slowly activating delayed-rectifier K(+) current (I(Ks)) that is important for action potential repolarization. Constitutive I(Ks) recorded from guinea-pig ventricular myocytes was suppressed by broad-spectrum tyrosine kinase (TK) inhibitors tyrphostin A23 (IC(50), 4.1+/-0.

CESE: Cell Electrophysiology Simulation Environment.

Unlabelled: Cell electrophysiology simulation environment (CESE) is an integrated environment for performing simulations with a variety of electrophysiological models that have Hodgkin-Huxley and Markovian formulations of ionic currents. CESE is written in Java 2 and is readily portable to a number of operating systems. CESE allows execution of single-cell models and modification and clamping of model parameters, as well as data visualisation and analysis using a consistent interface.

Cardiac Na+-Ca2+ exchanger current induced by tyrphostin tyrosine kinase inhibitors.

Tyrosine kinase (TK) inhibitors genistein and tyrphostin A23 (A23) inhibited Ca(2+) currents in guinea-pig ventricular myocytes investigated under standard whole-cell conditions (K(+)-free Tyrode's superfusate; EGTA-buffered (pCa-10.5) Cs(+) dialysate). However, the inhibitors (100 microM) also induced membrane currents that reversed between -40 and 0 mV, and the objective of the present study was to characterize these currents.

Transient outward current carried by inwardly rectifying K+ channels in guinea pig ventricular myocytes dialyzed with low-K+ solution.

There have been periodic reports of nonclassic (4-aminopyridine insensitive) transient outward K+ current in guinea pig ventricular myocytes, with the most recent one describing a novel voltage-gated inwardly rectifying type. In the present study, we have investigated a transient outward current that overlaps inward Ca2+ current (I(Ca,L)) in myocytes dialyzed with 10 mM K+ solution and superfused with Tyrode's solution. Although depolarizations from holding potential (Vhp) -40 to 0 mV elicited relatively small inward I(Ca,L) in these myocytes, removal of external K+ or addition of 0.

Selective block of swelling-activated Cl- channels over cAMP-dependent Cl- channels in ventricular myocytes.

The objective of this study on guinea-pig and rabbit ventricular myocytes was to evaluate the sensitivities of swelling-activated Cl- current (ICl(swell)) and cAMP-dependent cystic fibrosis transmembrane regulator (CFTR) Cl- current (ICl(CFTR)) to block by dideoxyforskolin and verapamil. The currents were recorded from whole-cell configured myocytes that were dialysed with a Cs+-rich pipette solution and superfused with either isosmotic Na+-, K+-, Ca2+-free solution that contained 140 mM sucrose or hyposmotic sucrose-free solution. Forskolin-activated ICl(CFTR) was inhibited by reference blocker anthracene-9-carboxylic acid but unaffected by < or = 200 microM dideoxyforskolin and verapamil.

Block of cardiac delayed-rectifier and inward-rectifier K+ currents by nisoldipine.

The objective of this study was to determine the concentration-dependent effects of nisoldipine, a dihydropyridine Ca2+ channel blocker, on K+ currents in guinea-pig ventricular myocytes. Myocytes in the conventional whole-cell configuration were bathed in normal Tyrode's solution or K+-free Tyrode's solution for the measurement of the effects of 0.01-100 microM nisoldipine on rapidly activating delayed-rectifier K+ current (I(Kr)), slowly activating delayed-rectifier K+ current (I(Ks)), inwardly rectifying K+ current (I(K1)), and reference L-type Ca2+ current (I(Ca,L)).