Spontaneous frequency of rabbit atrioventricular node myocytes depends on SR function.

Spontaneous Ca(2+) release from the sarcoplasmic reticulum (SR) appears to play an important role in cardiac sinoatrial node pacemaking. However, comparatively little is known about the role of intracellular Ca(2+) in the atrioventricular node (AVN). Intracellular Ca(2+) was therefore monitored in cells isolated from the rabbit AVN, using fluo-3 in conjunction with confocal microscopy.

Refining insights into high-affinity drug binding to the human ether-à-go-go-related gene potassium channel.

hERG (human ether-à-go-go-related gene) potassium (K(+)) channels play a crucial role in electrophysiological activity in the heart, exerting a profound influence on ventricular action potential repolarization and on the duration of the QT interval of the electrocardiogram. hERG channels are strongly implicated in the acquired form of long QT syndrome in that they exhibit a unique susceptibility to pharmacological inhibition by therapeutically and chemically diverse drugs. Investigations over a number of years provide compelling evidence that a comparatively large inner cavity and the presence of particular aromatic amino acid residues (Tyr652 and Phe656) on the inner (S6) helices of the channel are important features that allow hERG to accommodate and bind disparate drugs.

Treatment of dermatofibroma sarcoma protuberans using modified Mohs micrographic surgery: no recurrences and smaller defects.

Objectives: The purpose of this study was to evaluate the use of modified Mohs micrographic surgery (MMS) for dermatofibroma sarcoma protuberans (DFSP) in a single institution by a single surgeon.

Methods: The authors conducted a retrospective analysis of 25 patients with DFSP who were treated with modified MMS over the past 19 years at Scripps Clinic.

Results: Of the 25 patients treated with modified MMS for DFSP, there were no identifiable recurrences.

Computer three-dimensional reconstruction of the atrioventricular node.

Because of its complexity, the atrioventricular node (AVN), remains 1 of the least understood regions of the heart. The aim of the study was to construct a detailed anatomic model of the AVN and relate it to AVN function. The electric activity of a rabbit AVN preparation was imaged using voltage-dependent dye.

Anterior cervicoplasty: Neck rejuvenation using local anesthesia.

There is a subset of male patients that is troubled by redundant midline skin of the neck. Such patients may not be interested in having a face lift; they simply want elimination of the "turkey neck" appearance. Removal of redundant skin and underlying tissue can produce excellent results.

What specialties perform the most common outpatient cosmetic procedures in the United States?

Background: The number of cosmetic procedures performed annually is on the rise and is being performed by more specialties.

Purpose: We sought to determine the relative outpatient cosmetic procedure experience of dermatology and other specialties. We also examined demographic data of patients who underwent cosmetic procedures.

Repolarisation and vulnerability to re-entry in the human heart with short QT syndrome arising from KCNQ1 mutation--a simulation study.

Idiopathic short QT syndrome (SQTS) is a recently identified, genetically heterogeneous condition characterised by abbreviated QT intervals and an increased susceptibility to arrhythmia and sudden death. This simulation study identifies mechanisms by which cellular electrophysiological changes in the SQT2 (slow delayed rectifier, IKs, -linked) SQTS variant increases arrhythmia risk. The channel kinetics of the V307L mutation of the KCNQ1 subunit of the IKs channel were incorporated into human ventricular action potential (AP) models and into 1D and 2D transmural tissue simulations.

More types than one: multiple muscarinic receptor coupled K+ currents undergo remodelling in an experimental model of atrial fibrillation.

The common cardiac arrhythmia atrial fibrillation (AF) tends to show progression in its severity, which is associated with 'remodelling': structural and electrophysiological changes that facilitate arrhythmia induction and maintenance. In this issue of the BJP, Yeh and colleagues demonstrate for the first time, down-regulation of three types of muscarinic cholinergic receptor (mAChR) coupled K+ currents (IKM2, IKM3 and IKM4) and of M2, M3 and M4 mAChR subtype proteins, in a canine model of atrial tachycardia (AT) induced remodelling. The IKMs and their extent of AT-induced remodelling were similar in left-atrial and pulmonary vein (PV) myocytes, so remodelling of M2-M4 receptor-linked currents appears not to underlie the unique contribution of PVs to AF.

Differential pharmacology of the cardiac anionic background current I(AB).

A novel anionic background conductance (I(AB)) in cardiac ventricular myocytes has recently been identified but at present there is comparatively little information on its pharmacological modulation. This study investigated the effects of on I(AB) of four pyrethroid agents tefluthrin (a selective activator of this current), tetramethrin, fenpropathrin and alpha-cypermethrin in addition to other well known chloride channel modulators (chlorotoxin, gadolinium and picrotoxin). Guinea-pig ventricular myocytes were isolated using an enzymatic and mechanical dispersion procedure and all electrophysiological measurements were made using the whole-cell patch-clamp technique.

An outwardly rectifying anionic background current in atrial myocytes from the human heart.

This report describes a hitherto unreported anionic background current from human atrial cardiomyocytes. Under whole-cell patch-clamp with anion-selective conditions, an outwardly rectifying anion current (I(ANION)) was observed, which was larger with iodide than nitrate, and with nitrate than chloride as charge carrier. In contrast with a previously identified background anionic current from small mammal cardiomyocytes, I(ANION) was not augmented by the pyrethroid tefluthrin (10 microM); neither was it inhibited by hyperosmolar external solution nor by DIDS (200 microM); thus I(ANION) was not due to basal activity of volume-sensitive anion channels.

Inhibition of the HERG potassium channel by the tricyclic antidepressant doxepin.

HERG (human ether-à-go-go-related gene) encodes channels responsible for the cardiac rapid delayed rectifier potassium current, I(Kr). This study investigated the effects on HERG channels of doxepin, a tricyclic antidepressant linked to QT interval prolongation and cardiac arrhythmia. Whole-cell patch-clamp recordings were made at 37 degrees C of recombinant HERG channel current (I(HERG)), and of native I(Kr) 'tails' from rabbit ventricular myocytes.

The sodium channel Nav1.5a is the predominant isoform expressed in adult mouse dorsal root ganglia and exhibits distinct inactivation properties from the full-length Nav1.5 channel.

Nav1.5 is the principal voltage-gated sodium channel expressed in heart, and is also expressed at lower abundance in embryonic dorsal root ganglia (DRG) with little or no expression reported postnatally. We report here the expression of Nav1.

N- and C-terminal KCNE1 mutations cause distinct phenotypes of long QT syndrome.

Background: Long QT syndromes (LQTS) are inherited diseases involving mutations to genes encoding a number of cardiac ion channels and a membrane adaptor protein. The MinK protein is a cardiac K-channel accessory subunit encoded by the KCNE1 gene, mutations of which are associated with the LQT5 form of LQTS.

Objective: The purpose of this study was to search for the KCNE1 mutations and clarify the function of those mutations.

Treatment of severe cutaneous ulcerative lichen planus with low molecular weight heparin in a patient with hepatitis C.

The ulcerative variant of lichen planus (LP) commonly involves the oral mucosa but is uncommon and difficult to treat when located on other areas. We describe an unusual case of ulcerative LP involving several surfaces, including the palms and scrotum, in a 50-year-old man with hepatitis C. The patient was recalcitrant to treatment with conventional therapy but obtained clearance with a sustained response using low molecular weight heparin (LMWH).

Fellow-eye comparison of posterior capsule opacification rates after implantation of 1CU accommodating and AcrySof MA30 monofocal intraocular lenses.

Purpose: To measure posterior capsule opacification (PCO) and neodymium:YAG (Nd:YAG) capsulotomy rates between the AcrySof MA30 intraocular lens (IOL) (Alcon) and the 1CU IOL (HumanOptics) in a fellow-eye comparison.

Setting: Ophthalmology Department, St. Thomas' Hospital, London, United Kingdom.

Increased susceptibility to atrial tachyarrhythmia in spontaneously hypertensive rat hearts.

Although hypertension is the most prevalent risk factor for atrial fibrillation, there is currently no information available from animal models of hypertension regarding the development of atrial remodeling or increased susceptibility to atrial tachyarrhythmia. Therefore, we examined the susceptibility to atrial tachyarrhythmia and the development of atrial remodeling in excised perfused hearts from male spontaneously hypertensive rats in comparison with age-matched male Wistar-Kyoto normotensive controls at age 3 and 11 months, corresponding with early hypertension and pre-heart failure stages, respectively. The incidence and duration of left atrial tachyarrhythmia induced by burst pacing was greater in hearts from 11-month-old hypertensive animals than either in age-matched controls or in 3-month-old hypertensive rats, although there was no difference between hypertensive and normotensive hearts at 3 months.

hERG K+ channel blockade by the antipsychotic drug thioridazine: An obligatory role for the S6 helix residue F656.

The phenothiazine antipsychotic agent thioridazine has been linked with prolongation of the QT interval on the electrocardiogram, ventricular arrhythmias, and sudden death. Although thioridazine is known to inhibit cardiac hERG K(+) channels there is little mechanistic information on this action. We have investigated in detail hERG K(+) channel current (I(hERG)) blockade by thioridazine and identified a key molecular determinant of blockade.

Combined hERG channel inhibition and disruption of trafficking in drug-induced long QT syndrome by fluoxetine: a case-study in cardiac safety pharmacology.

Drug-induced prolongation of the rate-corrected QT interval (QTCI) on the electrocardiogram occurs as an unwanted effect of diverse clinical and investigational drugs and carries a risk of potentially fatal cardiac arrhythmias. hERG (human ether-à-go-go-related gene) is the gene encoding the alpha-subunit of channels mediating the rapid delayed rectifier K+ current, which plays a vital role in repolarising the ventricles of the heart. Most QTCI prolonging drugs can inhibit the function of recombinant hERG K+ channels, consequently in vitro hERG assays are used widely as front-line screens in cardiac safety-testing of novel chemical entities.

Objective measurement of intraocular lens movement and dioptric change with a focus shift accommodating intraocular lens.

Purpose: To objectively measure the shift and refractive change of the 1CU accommodating intraocular lens (IOL) (HumanOptics) and compare them to that of a monofocal AcrySof MA30 IOL (Alcon Laboratories) in the fellow eye.

Setting: Ophthalmology Department, St. Thomas' Hospital, London, United Kingdom.

Disopyramide is an effective inhibitor of mutant HERG K+ channels involved in variant 1 short QT syndrome.

The recently identified idiopathic short QT syndrome (SQTS) is associated with an increased risk of arrhythmia and sudden death. The use of implantable cardioverter defibrillators helps to protect SQTS patients from ventricular fibrillation; however, pharmacological treatments to normalise the QT interval are limited: thus far only quinidine has been found to be effective in a subset of patients, with the SQT1 variant. SQT1 is associated with an amino acid substitution (N588K) in the KCNH2-encoded HERG K(+) channel that reduces HERG current (I(HERG)) inactivation and sensitivity to drug block.

VEGF activates receptor-operated cation channels in human microvascular endothelial cells.

Objective: Vascular endothelial growth factor (VEGF) exerts many of its effects by stimulating endothelial calcium influx, but little is known about channels mediating VEGF-induced cation entry. The aim of this study was to measure and characterize for the first time the VEGF-activated cation current in human microvascular endothelial cells (HMVECs).

Methods And Results: Whole-cell patch-clamp recordings were made from HMVECs.

A TRPC-like non-selective cation current activated by alpha 1-adrenoceptors in rat mesenteric artery smooth muscle cells.

The TRPC family of non-selective cation channels has been suggested to play a key role in the responses to alpha1-adrenoceptor stimulation of vascular smooth muscle. However, there are still very few reports of non-selective cation currents activated by alpha1-AR in resistance arteries. Here, we examine the expression of TRPC channels and the currents activated by alpha1-adrenoceptors in rat mesenteric resistance artery smooth muscle.

Short QT syndrome.

The idiopathic short QT syndrome (SQTS) is a recently identified condition characterized by abbreviated QT intervals (typically 300 ms or less) and in affected families is associated with an increased incidence of atrial and ventricular arrhythmias and sudden cardiac death. Genetic analysis has, to date, identified three distinct forms of the condition, involving gain-of-function mutations to three different cardiac potassium channel genes: KCNH2 (SQT1), KCNQ1 (SQT2) and KCNJ2 (SQT3). This article reviews recent advances in understanding this syndrome, discussing the basis of QT interval shortening, possible mechanisms for the associated arrhythmogenic risk in SQT1, current approaches to treatment of the SQTS (focusing on SQT1) and avenues for future investigation.