Evaluation of genes encoding for the transient outward current (Ito) identifies the KCND2 gene as a cause of J-wave syndrome associated with sudden cardiac death.

Background: J-wave ECG patterns are associated with an increased risk of sudden arrhythmic death, and experimental evidence supports a transient outward current (I(to))-mediated mechanism of J-wave formation. This study aimed to determine the frequency of genetic mutations in genes encoding the I(to) in patients with J waves on ECG.

Methods And Results: Comprehensive mutational analysis was performed on I(to)-encoding KCNA4, KCND2, and KCND3 genes, as well as the previously described J-wave-associated KCNJ8 gene, in 51 unrelated patients with ECG evidence defining a J-wave syndrome.

Effects of the endogenous cannabinoid anandamide on voltage-dependent sodium and calcium channels in rat ventricular myocytes.

Background And Purpose: The endocannabinoid anandamide (N-arachidonoyl ethanolamide; AEA) exerts negative inotropic and antiarrhythmic effects in ventricular myocytes.

Experimental Approach: Whole-cell patch-clamp technique and radioligand-binding methods were used to analyse the effects of anandamide in rat ventricular myocytes.

Key Results: In the presence of 1-10 μM AEA, suppression of both Na(+) and L-type Ca(2+) channels was observed.

Effects of VPAC2 receptor activation on membrane excitability and GABAergic transmission in subparaventricular zone neurons targeted by suprachiasmatic nucleus.

The hypothalamic suprachiasmatic nucleus (SCN) harbors the master circadian pacemaker. SCN neurons produce the amino acid gamma-aminobutyric acid (GABA) and several peptide molecules for coordination and communication of their circadian rhythms. A subpopulation of SCN cells synthesizes vasoactive intestinal polypeptide (VIP) and provides a dense innervation of the subparaventricular zone (SPZ), an important CNS target of the circadian pacemaker.

Acid-sensitive TASK-like K+ conductances contribute to resting membrane potential and to orexin-induced membrane depolarization in rat thalamic paraventricular nucleus neurons.

Orexin (hypocretin) peptides are known to depolarize rat thalamic paraventricular nucleus (PVT) neurons by suppression of one or more undefined potassium conductances. Here, we investigated a contribution of TWIK-related acid-sensitive K(+) (TASK) channels to the resting membrane potential and orexin-induced depolarization of PVT neurons, using patch clamp recording techniques in brain slice preparations. Upon exposure to an acidic (pH 6.

Orexin-induced modulation of state-dependent intrinsic properties in thalamic paraventricular nucleus neurons attenuates action potential patterning and frequency.

The thalamic paraventricular nucleus (PVT) receives a dense innervation from orexin-synthesizing lateral hypothalamic neurons. Since PVT neurons display state-dependent tonic or low threshold spike-driven burst firing patterns, we examined how the response to exogenously applied orexins might modulate these features. Data were obtained with whole-cell patch clamp recording techniques in rat brain slices prepared during the subjective lights-on period.