Nanostimulation: manipulation of single neuron activity by juxtacellular current injection.

In the mammalian brain, many thousands of single-neuron recording studies have been performed but less than 10 single-cell stimulation studies. This paucity of single-cell stimulation data reflects a lack of easily applicable single-cell stimulation techniques. We provide a detailed description of the procedures involved in nanostimulation, a single-cell stimulation method derived from the juxtacellular labeling technique.

Fever-induced QTc prolongation and ventricular arrhythmias in individuals with type 2 congenital long QT syndrome.

Type 2 congenital long QT syndrome (LQT-2) is linked to mutations in the human ether a-go-go-related gene (HERG) and is characterized by rate-corrected QT interval (QTc) prolongation, ventricular arrhythmias, syncope, and sudden death. Recognized triggers of these cardiac events include emotional and acoustic stimuli. Here we investigated the repeated occurrence of fever-induced polymorphic ventricular tachycardia and ventricular fibrillation in 2 LQT-2 patients with A558P missense mutation in HERG.

Whisker movements evoked by stimulation of single motor neurons in the facial nucleus of the rat.

The lateral facial nucleus is the sole output structure whose neuronal activity leads to whisker movements. To understand how single facial nucleus neurons contribute to whisker movement we combined single-cell stimulation and high-precision whisker tracking. Half of the 44 stimulated neurons gave rise to fast whisker protraction or retraction movement, whereas no stimulation-evoked movements could be detected for the remainder.

Trafficking and functional expression of cardiac Na+ channels.

Voltage-gated Na(+)channels are essential for the amplitude and upstroke velocity of the cardiac action potential, which are important determinants for impulse propagation and impulse conduction velocity of throughout the working myocardium. Mutations in the major cardiac Na(+)channel gene SCN5A have been implicated in rare, familial forms of cardiac arrhythmias, namely LQT3, Brugada syndrome, progressive cardiac conduction disorder and sudden infant death syndrome. It is increasingly recognized that such mutations--apart from changing channel gating characteristics--may also be related to changes in channel protein trafficking and expression.

Na+ channel mutation leading to loss of function and non-progressive cardiac conduction defects.

Background: We previously described a Dutch family in which congenital cardiac conduction disorder has clinically been identified. The ECG of the index patient showed a first-degree AV block associated with extensive ventricular conduction delay. Sequencing of the SCN5A locus coding for the human cardiac Na+ channel revealed a single nucleotide deletion at position 5280, resulting in a frame-shift in the sequence coding for the pore region of domain IV and a premature stop codon at the C-terminus.

Compound heterozygosity for mutations (W156X and R225W) in SCN5A associated with severe cardiac conduction disturbances and degenerative changes in the conduction system.

Cardiac conduction defects associate with mutations in SCN5A, the gene encoding the cardiac Na+ channel. In the present study, we characterized a family in which the proband was born in severe distress with irregular wide complex tachycardia. His older sister died at 1 year of age from severe conduction disease with similarly widened QRS-complexes.