Influence of gelsolin deficiency on excitation contraction coupling in adult murine cardiomyocytes.

Ion channels involved in cardiac excitation-contraction coupling are linked to the cytoskeleton. Therefore changes in the cytoskeletal actin filaments may influence cardiac membrane currents and electro-mechanical coupling. Depolymerization of actin filaments by gelsolin (gsn) is involved in the organisation of the cytoskeleton by leading to a lower polymerization state.

High prevalence of peripheral arterial disease in patients with obstructive sleep apnoea.

Introduction: Obstructive sleep apnoea (OSA) merits increasing attention as cardiovascular risk factor. Whereas carotid and coronary artery disease have been associated with OSA, occurrence of peripheral arterial disease (PAD) in OSA remains undefined.

Methods: We screened 100 patients with suspected OSA for PAD.

Prevalence and clinical relevance of the morphological substrate of ventricular arrhythmias in patients without known cardiac conditions detected by cardiovascular MR.

Objective: Cardiac MR (CMR) identifies the substrate of ventricular arrhythmia (VA) in cardiomyopathies and coronary heart disease. However, little is known about the value of CMR in patients with VA without previously known cardiac disorders.

Methods: 76 patients with VA (Lown ≥2) without known cardiac disease after regular diagnostic work-up were studied with CMR, and findings were correlated with electrocardiogram (ECG) and electrophysiological stimulation (EPS).

CaMKII negatively regulates calcineurin-NFAT signaling in cardiac myocytes.

Rationale: Pathological cardiac myocyte hypertrophy is thought to be induced by the persistent increases in intracellular Ca(2+) needed to maintain cardiac function when systolic wall stress is increased. Hypertrophic Ca(2+) binds to calmodulin (CaM) and activates the phosphatase calcineurin (Cn) and CaM kinase (CaMK)II. Cn dephosphorylates cytoplasmic NFAT (nuclear factor of activated T cells), inducing its translocation to the nucleus where it activates antiapoptotic and hypertrophic target genes.

Two-photon laser scanning microscopy of the transverse-axial tubule system in ventricular cardiomyocytes from failing and non-failing human hearts.

Objective. The transverse-axial tubule system (TATS) of cardiomyocytes allows a spatially coordinated conversion of electrical excitation into an intracellular Ca(2+) signal and consequently contraction. Previous reports have indicated alterations of structure and/or volume of the TATS in cardiac hypertrophy and failure, suggesting a contribution to the impairment of excitation contraction coupling.

Age and hypertrophy related changes in contractile post-rest behavior and action potential properties in isolated rat myocytes.

"Physiological" aging as well as early and progressive cardiac hypertrophy may affect action potential (AP) pattern, contractile function, and Ca(2+) handling. We hypothesize that contractile function is disturbed in hypertrophy from early stages and is differently affected in aged myocardium. In vivo function, cardiomyocyte contractile behavior and APs were compared in Wistar-Kyoto (WIS) rats and spontaneously hypertensive rats (SHR) at different ages and degrees of hypertrophy (3-4, 9-11, 20-24 months).

Pacemaking by HCN channels requires interaction with phosphoinositides.

Hyperpolarization-activated, cyclic-nucleotide-gated (HCN) channels mediate the depolarizing cation current (termed I(h) or I(f)) that initiates spontaneous rhythmic activity in heart and brain. This function critically depends on the reliable opening of HCN channels in the subthreshold voltage-range. Here we show that activation of HCN channels at physiologically relevant voltages requires interaction with phosphoinositides such as phosphatidylinositol-4,5-bisphosphate (PIP(2)).

The Na+/Ca2+ exchanger/SR Ca2+ ATPase transport capacity regulates the contractility of normal and hypertrophied feline ventricular myocytes.

Background: Pressure overload leads to cardiac hypertrophy, which is often followed by heart failure. We tested the hypothesis that depressed contractility in this process results from an imbalance in Ca 2+ transport by the sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA) and the sarcolemmal Na+/Ca2+ exchanger (NCX).

Methods And Results: Left ventricular (LV) myocytes (n = 79) from 12 normal (N) and 5 hypertrophied (LVH, by aortic banding) feline hearts were studied.

Method-related effects of adenovirus-mediated LacZ and SERCA1 gene transfer on contractile behavior of cultured failing human cardiomyocytes.

Introduction: Adenovirus-mediated gene transfer into cardiomyocytes has emerged as an interesting tool to study functional effects of single proteins. However, the functional consequences of cell isolation, cell culture per se and adenovirus-mediated transfer of the LacZ or SERCA1 gene in failing human cardiomyocytes warrant further investigation.

Methods: Primary cell culture was performed without or after adenovirus-mediated gene transfer of LacZ or SERCA1.

Calcium entry via Na/Ca exchange during the action potential directly contributes to contraction of failing human ventricular myocytes.

Unlabelled: Prolongation of the Ca2+ transient and action potential (AP) durations are two characteristic changes in myocyte physiology in the failing human heart. The hypothesis of this study is that Ca2+ influx via reverse mode Na+/Ca2+ exchanger (NCX) or via L-type Ca2+ channels directly activates contraction in failing human myocytes while in normal myocytes this Ca2+ is transported into the sarcoplasmic reticulum (SR) to regulate SR Ca2+ stores.

Methods: Myocytes were isolated from failing human (n=6), nonfailing human (n=3) and normal feline hearts (n=9) and whole cell current and voltage clamp techniques were used to evoke and increase the duration of APs (0.

Cellular basis of abnormal calcium transients of failing human ventricular myocytes.

Depressed contractility is a central feature of the failing human heart and has been attributed to altered [Ca2+]i. This study examined the respective roles of the L-type Ca2+ current (ICa), SR Ca2+ uptake, storage and release, Ca2+ transport via the Na+-Ca2+ exchanger (NCX), and Ca2+ buffering in the altered Ca2+ transients of failing human ventricular myocytes. Electrophysiological techniques were used to measure and control V(m) and measure I(m), respectively, and Fluo-3 was used to measure [Ca2+]i in myocytes from nonfailing (NF) and failing (F) human hearts.