Pathways of HERG inactivation.

The rapid, repolarizing K(+) current in cardiomyocytes (I(Kr)) has unique inwardly rectifying properties that contribute importantly to the downstroke of the cardiac action potential. The human ether-à-go-go-related gene (HERG) expresses a macroscopic current virtually identical to I(Kr), but a description of the single-channel properties that cause rectification is lacking. For this reason we measured single-channel and macropatch currents heterologously expressed by HERG in Xenopus oocytes.

Cloning and expression of a novel member of the low voltage-activated T-type calcium channel family.

Low voltage-activated Ca2+ channels play important roles in pacing neuronal firing and producing network oscillations, such as those that occur during sleep and epilepsy. Here we describe the cloning and expression of the third member of the T-type family, alpha1I or CavT.3, from rat brain.

Molecular characterization of a neuronal low-voltage-activated T-type calcium channel.

The molecular diversity of voltage-activated calcium channels was established by studies showing that channels could be distinguished by their voltage-dependence, deactivation and single-channel conductance. Low-voltage-activated channels are called 'T' type because their currents are both transient (owing to fast inactivation) and tiny (owing to small conductance). T-type channels are thought to be involved in pacemaker activity, low-threshold calcium spikes, neuronal oscillations and resonance, and rebound burst firing.

Interactions of the nonsedating antihistamine loratadine with a Kv1.5-type potassium channel cloned from human heart.

The use of nonsedating antihistamines may, on rare occasions, be associated with cardiac arrhythmias. This could be due to blockade of voltage-dependent K+ channels in the heart, leading to a prolongation in repolarization in the human myocardium. For this reason, we examined the effects of the nonsedating antihistamine loratadine on a rapidly activating delayed-rectifier K+ channel (Kv1.

[A cost-benefit evaluation of prenatal diagnosis performed at a referral center with a population with a genetic or abnormality risk].

Prenatal diagnosis (PND) has assistencial, psychological and economical consequences; it is very important to evaluate cost effectiveness for the population. A prospective study was done (longitudinal and descriptive) on a population referred to Maternidade Dr. Alfredo da Costa, divided into two groups.

[Incessant atrial tachycardia and peripartum cardiomyopathy--a therapeutic challenge].

Peripartum cardiomyopathy is an uncommon cause of heart failure but with serious prognosis. We report the case of a patient with peripartum cardiomyopathy presenting acute heart failure (severe biventricular systolic failure) and incessant atrial tachycardia, a rare arrhythmia difficult to control, that was responsible for cardiogenic shock, fetus death and multiple organ failure: renal failure (hemodialysis during 17 days), respiratory and hepatic failure and ischemic acute cholecystitis (treated surgically). After emergency cesarean section, heart rate control was obtained only after administering verapamil.

Molecular physiology and pharmacology of HERG. Single-channel currents and block by dofetilide.

Background: The human ether-a-go-go-related gene (HERG) is one locus for the hereditary long-QT syndrome. A hypothesis is that HERG produces the repolarizing cardiac potassium current IKr with the consequence that mutations in HERG prolong the QT interval by reducing IKr. The elementary properties of HERG are unknown, and as a test of the hypothesis that HERG produces IKr, we compared their elementary properties.

[Electrocardiographic changes after coronary angiography: effect of the contrast media used].

Unlabelled: Prospective study to evaluate the influence of 2 different iodine contrasts (used in coronariography) on the electrocardiographic changes recorded after intra-coronary injection.

Material And Methods: Sixty-six patients (pts) - 50 men and 16 women - 59 +/- 4 years underwent coronariography to confirm and/or evaluate coronary artery disease (CAD). Group I (33 pts) received a hyperosmolar contrast; group II received a low osmolarity contrast.

Mapping the block of a cloned human inward rectifier potassium channel by dofetilide.

Dofetilide, a methanesulfonanilide derivative, is a potent class III antiarrhythmic drug. Like other members of this class of K+ channel blockers, the sites in the channel to which the drug binds are unknown, although high and low affinity binding has been reported in cardiomyocytes. The most sensitive K+ channel target for dofetilide seems to be IKr, the rapid component of the repolarizing delayed rectifier K+ current.

[The imaging of malignant pancreatic tumors].

Malignant neoplasias of the pancreas include various histological types with imaging characteristics and behaviour which allows them to be distinguished from one another in a good percentage of situations. However, differentiation is not always possible without resorting to anatomo-pathological techniques, differential diagnosis with benign lesions being a great challenge to imaging, with particular reference to the inflammatory masses. Adenocarcinoma makes up about 95% of pancreatic neoplasias and is one of the great causes of death by cancer in developed countries.

Voltage-dependent inactivation in a cardiac-skeletal chimeric calcium channel.

The loci for inactivation in calcium channel proteins are unknown. Mechanisms for inactivation may be distributed across Ca2+ channel subunits and appear to be complex, multiple and interacting. We took advantage of the properties of chimeras, constructed between cardiac (H4) and skeletal muscle (Sk4) calcium channel alpha 1 subunits to study the molecular mechanism of inactivation in L-type calcium channels.

T-type and N-type calcium channels of Xenopus oocytes: evidence for specific interactions with beta subunits.

We used amplifying effects of calcium channel beta subunits to identify endogenous calcium channels in Xenopus oocytes. Expression of rat brain beta 4 increased macroscopic endogenous current magnitude with a small effect on kinetics. In contrast, expression of rat brain/cardiac beta 2 produced a much larger increase in current magnitude and dramatically slowed current decay.

Modification of Ca2+ channel activity by deletions at the carboxyl terminus of the cardiac alpha 1 subunit.

Voltage-sensitive Ca2+ channels are multisubunit complexes that include, among others, a large alpha 1 subunit, which by itself is sufficient to form a channel. Several alpha 1 genes encoding L-, N-, and P-type Ca2+ channels have been cloned. These alpha 1 genes share a high degree of sequence homology in the putative transmembrane regions, but vary substantially in the putative intracellular loops and the flanking amino and carboxyl termini.