Stretch-activated currents in ventricular myocytes: amplitude and arrhythmogenic effects increase with hypertrophy

Kamkin, Andre; Kiseleva, Irina; Isenberg, Gerrit

doi:10.1016/s0008-6363(00)00208-x

Cited by 146 publications

(162 citation statements)

References 37 publications

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“…Axial stretch did not increase I Ca,L , the major pathway for the generation of depolarising current dependent upon Ca 2+ (consistent with previous reports under different experimental conditions; White, 1995;Hongo et al 1996;Kamkin et al 2000). However, the observation that the effect of stretch on the APD was abolished by buffering of [Ca 2+ ] i with BAPTA strongly supports the hypothesis that Ca 2+ modulation plays a major role in the electrical response of cardiac muscle to stretch.…”

Section: Journal Of Physiologysupporting

confidence: 90%

“…In contrast to our varied observation of SACs, the stretchinduced prolongation of the free APD was consistently observed. In addition, although the current-voltage relationship of the SACs predicts lengthening of APD at 90 % repolarisation, it predicts shortening at 20 % repolarisation; thus it seems SACs cannot fully explain the effect of stretch on the free action potential and additional mechanisms are involved.Axial stretch did not increase I Ca,L , the major pathway for the generation of depolarising current dependent upon Ca 2+ (consistent with previous reports under different experimental conditions; White, 1995;Hongo et al 1996;Kamkin et al 2000). However, the observation that the effect of stretch on the APD was abolished by buffering of [Ca 2+ ] i with BAPTA strongly supports the hypothesis that Ca 2+ modulation plays a major role in the electrical response of cardiac muscle to stretch.…”

supporting

confidence: 90%

“…Stretchinduced alteration of the action potential waveform and initiation of extra-systoles has been reported in single cells (Kamkin et al 2000), multicellular and whole-heart preparations (Franz et al 1989(Franz et al , 1992. These disturbances in electrical activity of the myocardium have been linked to clinically observed arrhythmias (Lab, 1999).…”

mentioning

confidence: 99%

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Streptomycin and intracellular calcium modulate the response of single guinea‐pig ventricular myocytes to axial stretch

Belus

White

2003

The Journal of Physiology

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Isolation of guinea-pig ventricular myocytesGuinea-pigs (weight approximately 300 g) were killed by cervical dislocation following stunning; all procedures conformed with the UK Animals (Scientific Procedures) Act 1986. Left ventricular myocytes were isolated using methods based on those of Frampton et al. (1991). Briefly, hearts were removed and mounted on a Langendorff apparatus and perfused with a Hepes-based isolation solution of the following composition (mM): NaCl 130; KCl 5.4; NaH 2 PO 4 0.4; MgCl 2 .6H 2 O 1.4; CaCl 2 1.8; Hepes 10; glucose 10; taurine 20; creatine 10; with 1 % bovine serum albumin (pH 7.3) to clear blood from the coronary circulation. Perfusion was then continued with Ca 2+ -free isolation solution Streptomycin and intracellular calcium modulate the response of single guinea-pig ventricular myocytes to axial stretch Alexandra Belus and Ed White School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UKWe tested the hypothesis that both stretch-activated channels (SACs) and intracellular calcium ([Ca 2+ ] i ) are important in the electrical response of single guinea-pig ventricular myocytes to axial stretch. Myocytes were attached to carbon fibre transducers and stretched, sarcomere length increased by approximately 9 %, and there was a prolongation of the action potential duration. Streptomycin, a blocker of SACs, had no effect upon the shortening, [Ca 2+ ] i transients or action potentials of electrically stimulated, unstretched myocytes, at a concentration of 50 mM, but at 40 mM, prevented any stretch-induced increase in action potential duration. Under action potential clamp, stretch elicited a current with a linear current-voltage relationship that was inward at membrane potentials negative to its reversal potential of _30 mV, in 10 of 24 cells tested, and was consistent with the activation of non-specific, cationic SACs. This current was not seen in any stretched cells that were exposed to 40 mM streptomycin. However, exposure of cells to 5 mM BAPTA-AM, in order to reduce [ Journal of Physiology(1.8 mM CaCl 2 replaced with 0.1 mM EGTA) for 4 min, followed by 5 min perfusion with isolation solution containing 50 mM Ca 2+ , 1 mg ml _1 collagenase (type II; Worthington Biochemical Corporation, NJ, USA) and 0.1 mg ml _1 protease (type XIV; Sigma Chemical Co.). The left ventricle was then separated from the rest of the heart, minced, and gently shaken at 37°C in the collagenase-containing isolation solution. Cells were filtered from this solution at 5 min intervals and resuspended in isolation solution containing 1.8 mM Ca 2+ .To ] i were measured simultaneously. A video image of the cell was monitored using an edge detection system (Crescent Electronics, UT, USA) and the change in cell length following stimulation was used as our measure of contractility. Cells were loaded with the Ca 2+ -sensitive fluorescent indicator fura-2 AM (Molecular Probes, OR, USA) by incubation for 10 min at 22-24° C in 1.8 mM Ca 2+ isolation solution containing 3-5 mM fura-2 AM. The ratio of fl...

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Section: Journal Of Physiologysupporting

confidence: 90%

supporting

confidence: 90%

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Streptomycin and intracellular calcium modulate the response of single guinea‐pig ventricular myocytes to axial stretch

Belus

White

2003

The Journal of Physiology

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“…When fiber tension remains uncompensated or simply unbalanced, it may represent a trigger for arrhythmogenesis caused by cytoskeletal stretching, which ultimately leads to altered ion channel localization, and subsequent action potential and conduction alterations. 9 Cytoskeletal proteins not only provide the backbone of the cellular structure, but they also maintain the shape and flexibility of the different sub-cellular compartments, including the plasma membrane, the double lipid layer, which defines the boundaries of the cell and where ion channels are mainly localized. The interaction between the sarcomere, which is the basic contractile unit of striated muscles, and the sarcolemma, the plasma membrane surrendering the muscle fibers in skeletal muscle and the muscle cell of the cardiomyocyte, determines the mechanical plasticity of the cell, enabling it to complete and re-initiate each contractionrelaxation cycle.…”

Section: The Sarcomerementioning

confidence: 99%

Cytoskeletal Basis of Ion Channel Function in Cardiac Muscle

Vatta

Faulkner

2006

Future Cardiol.

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SummaryThe heart is a force-generating organ that responds to self-generated electrical stimuli from specialized cardiomyocytes. This function is modulated by sympathetic and parasympathetic activity.In order to contract and accommodate the repetitive morphological changes induced by the cardiac cycle, cardiomyocytes depend on their highly evolved and specialized cytoskeletal apparatus. Defects in components of the cytoskeleton, in the long term, affect the ability of the cell to compensate at both functional and structural levels. In addition to the structural remodeling, the myocardium becomes increasingly susceptible to altered electrical activity leading to arrhythmogenesis. The development of arrhythmias secondary to structural remodeling defects has been noted, although the detailed molecular mechanisms are still elusive. Here I will review the current knowledge of the molecular and functional relationships between the cytoskeleton and ion channels and, I will discuss the future impact of new data on molecular cardiology research and clinical practice.

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“…TRPC1 and TRPC6 are ubiquitously expressed in whole myocardial tissues (Huang et al, 2009;Ward et al, 2008), and GsMTx-4 suppresses stretch-induced force development and concomitant [Ca 2+ ] i increase in mouse left ventricular trabecular muscle (Ward et al, 2008) and pressureinduced atrial fibrillation (Franz and Bode, 2003). Moreover, the expression of TRPC1 and TRPC6 is greatly increased in hypertrophied heart under prolonged pressure overload (Kuwahara, et al;Ohba, et al, 2007), where the susceptibility to mechanically-induced arrhythmia is also enhanced (Kamkin et al, 2000a). All these observations favor the view that TRPC1 and TRPC6 contribute to stretch-induced arrhythmias as MSCCs in some pathological settings.…”

Section: Stretch-induced Arrhythmia In Pathological Settingsmentioning

confidence: 99%