Dominant-negative suppression of HCN channels markedly reduces the native pacemaker current I(f) and undermines spontaneous beating of neonatal cardiomyocytes.

Background: The pacemaker current I(f) contributes to spontaneous diastolic depolarization of cardiac autonomic cells. In heterologous expression, HCN channels exhibit a hyperpolarization-activated inward current similar to I(f). However, the links between HCN genes and native I(f) are largely inferential, and it remains unknown whether I(f) is essential for cardiac pacing.

Ca2+-handling in heart failure--a review focusing on Ca2+ sparks.

[Ca2+]i-transients have been shown to be altered in isolated ventricular myocytes from terminally failing human myocardium. It has been demonstrated that one reason for this alteration is a reduction in the Ca2+ content of the sarcoplasmic reticulum (SR). Further investigations were done to investigate, whether there may be an additional defect of the Ca2+-release mechanisms from the SR.

[Hormonal hyperactivity in heart failure. Differences in beta blockers].

Pathophysiology: Heart failure is characterized by a disturbed contractility and activation of neurohumoral mechanisms. Activation of the adrenergic system and the beta-adrenergic signal transduction pathway leads to downregulation of beta 1-receptors of the heart muscle cell membrane.

Therapy: In addition to ACE inhibitors, diuretics and glycosides, beta blockers are an integral part in the combination therapy of patients with heart failure.

Identification of gating modes in single native Na+ channels from human atrium and ventricle.

The aim of the present study was to investigate the single-channel properties of different gating modes in the native human cardiac Na+ channel. Patch-clamp experiments were performed at low noise using ultrathick-walled pipettes. In 17 cell-attached patches containing only one channel, fast back and forth switching between five different Na+-channel gating modes (F-mode, M1-mode, M2-mode, S-mode, and P-mode) was identified, but no difference in the gating properties was found between normal and diseased cardiomyocytes from atrium or ventricle, respectively.