Selected Contribution: Axial stretch  increases spontaneous pacemaker activity  in rabbit isolated sinoatrial node cells

Cooper, Patricia J; Lei, Ming; Cheng, Long; Kohl, Peter

doi:10.1152/jappl.2000.89.5.2099

Cited by 81 publications

(68 citation statements)

References 24 publications

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“…The contribution of I f and its importance as a pharmaceutical target has been proven by the successful development of ivabradine and is delineated further in the review article by DiFrancesco 26 in this review series. Further currents seem to be involved in the depolarization phase (I st , mechanosensitive currents 27 and others) whose relative contributions are still to be determined.…”

Section: Discussionmentioning

confidence: 99%

Competing Oscillators in Cardiac Pacemaking

Noble

Fink

2010

Circulation Research

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Key Words: cardiac pacemaker Ⅲ heart models Ⅲ calcium oscillator Ⅲ membrane oscillator T he earliest models of cardiac rhythm, beginning with that of Noble, 1 were restricted to interactions between surface membrane ion channels. The first cardiac cell model to incorporate the intracellular calcium signaling system involved in excitation-contraction coupling was that of DiFrancesco and Noble. 2 That model was developed for sheep Purkinje fibers, and it was the first to predict a large role for sodium/calcium exchange current during the action potential. In fact it identified the slower components of inward current that had previously been attributed to calcium channel current as being attributable instead to the exchanger. Pacemaker activity in that model was attributed almost entirely to the slow onset of the nonspecific cation current, i f, activated by hyperpolarization. The exchange current was not predicted to play any role in pacemaker rhythm in that case.However, the DiFrancesco-Noble Purkinje fiber model was almost immediately developed to create the first mathematical model to reproduce voltage waveforms similar to those observed in rabbit sinoatrial node (SAN) cells. 3 It was also developed later to create the first models of rabbit atrial cells. 4,5 For the intracellular calcium signaling mechanisms, the 1980s models were based on the work of Fabiato on calcium-induced calcium release. 6 The experimental basis of the SAN model was the work of Brown et al, 7,8 which revealed the presence of very slow components of inward current similar to that predicted for the Original

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Section: Discussionmentioning

confidence: 99%

Competing Oscillators in Cardiac Pacemaking

Noble

Fink

2010

Circulation Research

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“…One potential limitation of our study is whether the mechanical perturbations may be affecting small numbers of pacemaker cells that may have been present in the cell monolayers (although we isolated cells from only the bottom 70% of the ventricle). It may be argued that the pacemaking ability of these cells would be suppressed by the large electrical load presented by surrounding ventricular cells but that mechanical perturbations may augment the pacemaker activity, as underlies the Bainbridge reflex to stretch and has been observed in isolated sinoatrial nodal tissue (1) and isolated sinoatrial nodal cells (11). However, in the former study, the tissue was stretched by an unspecified length for a period of 5 s, whereas in the latter study cell length was increased by 5-10% of resting length and held for the duration of measurements (time interval unspecified).…”

Section: Discussionmentioning

confidence: 99%

Mechanoelectrical excitation by fluid jets in monolayers of cultured cardiac myocytes

Kong

Bursac

Tung³

2005

Journal of Applied Physiology

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Kong, Chae-Ryon, Nenad Bursac, and Leslie Tung. Mechanoelectrical excitation by fluid jets in monolayers of cultured cardiac myocytes. J Appl Physiol 98: 2328 -2336, 2005. First published February 24, 2005 doi:10.1152/japplphysiol.01084.2004.-Although the prevailing view of mechanoelectric feedback (MEF) in the heart is in terms of longitudinal cell stretch, other mechanical forces are considerable during the cardiac cycle, including intramyocardial pressure and shear stress. Their contribution to MEF is largely unknown. In this study, mechanical stimuli in the form of localized fluid jet pulses were applied to neonatal rat ventricular cells cultured as confluent monolayers. Such pulses result in pressure and shear stresses (but not longitudinal stretch) in the monolayer at the point of impingement. The goal was to determine whether these mechanical stimuli can trigger excitation, initiate a propagated wave, and induce reentry. Cells were stained with the voltage-sensitive dye RH237, and multi-site optical mapping was used to record the spread of electrical activity in isotropic and anisotropic monolayers. Pulses (10 ms) with velocities ranging from 0.3 to 1.8 m/s were applied from a 0.4-mm diameter nozzle located 1 mm above the cell monolayer. Fluid jet pulses resulted in circular wavefronts that propagated radially from the stimulus site. The likelihood for mechanical stimulation was quantified as an average stimulus success rate (ASSR). ASSR increased with jet amplitude and time waited between stimuli and decreased with the application of gadolinium and streptomycin, blockers of stretch-activated channels, but not with nifedipine, a blocker of the L-type Ca channel. Absence of cellular injury was confirmed by smooth propagation maps and propidium iodide stains. In rare instances, the mechanical pulse resulted in the induction of reentrant activity. We conclude that mechanical stimuli other than stretch can evoke action potentials, propagated activity, and reentrant arrhythmia in two-dimensional sheets of cardiac cells. mechanoelectrical coupling; ventricular arrhythmias; optical mapping; cell culture; neonatal rat NUMEROUS STUDIES have shown that mechanical stretch or load applied to a cardiac tissue can induce significant electrophysiological effects via the process termed "mechanoelectric feedback" (MEF). Mechanically triggered action potentials have been observed with sudden stretch of the ventricles (20), stretch of the isolated ventricular free wall (17), or mechanical stimulation of single cardiac myocytes (13,28,42). Mechanical stretch also changes action potential duration (42, 48, 51), excitability (45), and expression of gap junctional channels (52). The electrophysiological effects have been attributed mainly to the activity of stretch-activated ion channels (SACs) (26). Pharmacological agents that inhibit SAC activity include streptomycin (21), gadolinium (Gd 3ϩ ) (26), and the tarantula toxin .The mechanically induced premature ventricular beats mentioned above can be proarrhythmic. As a dramati...

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“…This SAC model was described in detail in our recent work (39). Several studies have shown that physical stretch of isolated ventricular myocytes produced stretch-activated currents with a linear current/voltage relationship and reversal potentials between Ϫ6 and Ϫ11 mV (6,48,49). Thus, for the majority of experiments in this study, we set the reversal potential of SAC (E SAC) ϭ Ϫ10 mV and GSAC to a constant value for each recording, but the value of GSAC was varied to investigate the critical GSAC required to induce EADs.…”

Section: Methodsmentioning

confidence: 99%

Stretch-activated channel activation promotes early afterdepolarizations in rat ventricular myocytes under oxidative stress

Wang¹,

Joyner²,

Wagner³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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BH. Stretch-activated channel activation promotes early afterdepolarizations in rat ventricular myocytes under oxidative stress. Am J Physiol Heart Circ Physiol 296: H1227-H1235, 2009. First published March 13, 2009 doi:10.1152/ajpheart.00808.2008.-Mechanical stretch and oxidative stress have been shown to prolong action potential duration (APD) and produce early afterdepolarizations (EADs). Here, we developed a simulation model to study the role of stretch-activated channel (SAC) currents in triggering EADs in ventricular myocytes under oxidative stress. We adapted our coupling clamp circuit so that a model ionic current representing the actual SAC current was injected into ventricular myocytes and added as a real-time current. This current was calculated as ISAC ϭ GSAC ‫ء‬ (Vm Ϫ ESAC), where GSAC is the stretch-activated conductance, Vm is the membrane potential, and ESAC is the reversal potential. In rat ventricular myocytes, application of GSAC did not produce sustained automaticity or EADs, although turn-on of GSAC did produce some transient automaticity at high levels of GSAC. Exposure of myocytes to 100 M H2O2 induced significant APD prolongation and increase in intracellular Ca 2ϩ load and transient, but no EAD or sustained automaticity was generated in the absence of GSAC. However, the combination of GSAC and H2O2 consistently produced EADs at lower levels of GSAC (2.6 Ϯ 0.4 nS, n ϭ 14, P Ͻ 0.05). Pacing myocytes at a faster rate further prolonged APD and promoted the development of EADs. SAC activation plays an important role in facilitating the development of EADs in ventricular myocytes under acute oxidative stress. This mechanism may contribute to the increased propensity to lethal ventricular arrhythmias seen in cardiomyopathies, where the myocardium stretch and oxidative stress generally coexist. arrhythmia mechanisms; action potential; patch clamp PREVIOUS STUDIES HAVE SHOWN that myocardial stretch, a process termed "mechanoelectric feedback," can induce myocyte depolarization and abnormal impulses by the stretch-activated channel (SAC) currents (7,21). A subset of SACs has been reported as nonselective cation channels (48), which allow Na ϩ , K ϩ , Cs ϩ , and Ca 2ϩ to permeate (36). A linear currentvoltage relationship has been described for SACs with reversal potentials measured in myocytes from Ϫ6 to Ϫ15 mV (17,33,48). In a review by Kohl et al. (24), they note that models incorporating SACs as pure charge carriers and models that include movement of ions through the channels both reproduced experimental phenomena, such as diastolic depolarization, positive chronotropic responses of pacemakers, and action potential (AP) generation due to stretch (25).It has been suggested that oxidative stress is a mechanism for Ca 2ϩ overload and the consequent electrical changes in cardiomyocytes (5). On the other hand, Ca 2ϩ overload increases oxidative stress by altering mitochondrial function, which leads to increased production of oxygen radicals (9). Oxidative stress alters the function of several elem...

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Selected Contribution: Axial stretch increases spontaneous pacemaker activity in rabbit isolated sinoatrial node cells

Cited by 81 publications

References 24 publications

Competing Oscillators in Cardiac Pacemaking

Competing Oscillators in Cardiac Pacemaking

Mechanoelectrical excitation by fluid jets in monolayers of cultured cardiac myocytes

Stretch-activated channel activation promotes early afterdepolarizations in rat ventricular myocytes under oxidative stress

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