Rate-dependency of Action Potential Duration and Refractoriness in Isolated Myocytes from the Rabbit AV Node and Atrium

Workman, Antony J.; Kane, Kathleen A.; Rankin, Andrew C.

doi:10.1006/jmcc.2000.1186

Cited by 15 publications

(20 citation statements)

References 42 publications

(58 reference statements)

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“…One of these is the complete lack of evidence for transient outward K + current (I to ) in voltage-clamp measurements in the study. This is consistent with the general lack of I to in guinea-pig cardiac myocytes, but contrasts with the situation in the rabbit AVN, in which I to is present in a proportion of cells [31] and exhibits kinetics that may allow it to contribute to AP repolarisation [30,32], although there is some evidence against a role for I to in the APD-rate relation [44]. The absence of an I to in our experiments suggests that, in the guinea-pig at least, this current is not required for functional AVN activity and that AP repolarisation is mediated entirely by other outward conductances.…”

Section: Comparison With Previous Studiessupporting

confidence: 68%

“…However, in the 1970s the morphology of the rabbit AVN was described in detail [1,2] and from the early 1980s onwards the rabbit has been the species of choice for the isolation of single AVN cells for electrophysiological study. Studies of rabbit isolated AVN cells have provided information on the characteristics and potential roles of various ionic currents present [14,15,17,23,24,25,29,30,31,32,33,42,44], and on the actions of clinically used agents including adenosine [24,25,42,43] and various antiarrhythmic drugs [16,29,30,36]. Recent experiments on cell-to-cell coupling have utilised isolated AVN myocytes from the rabbit heart [21,39].…”

Section: Introductionmentioning

confidence: 98%

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Characteristics of single cells isolated from the atrioventricular node of the adult guinea-pig heart.

Yuill¹,

Hancox²

2002

Pfl�gers Archiv European Journal of Physiology

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To date, data regarding the cellular electrophysiology of the atrioventricular node (AVN) have derived from AVN cells isolated from the rabbit heart. The aim of this study was to characterise for the first time the electrophysiological properties of single cells isolated from the AVN of the guinea-pig heart. Cells were isolated from the AVN region by a combination of enzymatic and mechanical dispersion. Mean (+/-SEM) cell dimensions were 110.8+/-2.3 microm in length by 11.4+/-1.3 micro m in width (n=76 cells). Electrophysiological recordings were made using the whole-cell patch-clamp technique at 37 degrees C. Mean cell capacitance was 25.1+/-0.9 pF (n=43) and mean cell input resistance was 1,377+/-178 Muomega (n=21). Spontaneously active cells exhibited action potentials characteristic of cardiac pacemaker tissue. Under whole-cell voltage clamp, the mean 'zero current' potential was -39.7+/-4.1 mV (n=21). Voltage commands of 500 ms duration to a range of test potentials from a holding potential of -40 mV revealed a number of distinct current components. At potentials positive to -40 mV an early inward current was observed that exhibited a bell-shaped current voltage (I-V) relation, typical of L-type calcium current. A delayed outward current that increased progressively with test potential magnitude was also observed. Analysis of the outward current 'tails' on repolarisation to -40 mV showed this to be comprised of two components with half-maximal activation voltages of -17.2+/-1.8 mV, and +27.1+/-3.6 mV (n=13). 'Transient outward' current appeared absent from guinea-pig AVN cells. Hyperpolarising test pulses activated net inward current, for which three components could be observed: a barium-sensitive (100 microM Ba(2+)) inwardly rectifying current evident at the start of the voltage command and prominent at potentials negative to the diastolic potential range; a time-dependent, hyperpolarisation-activated current, and a residual background current. On repolarisation to -40 mV, a large inward current spike typical of cardiac Na current was observed in some cells. Notably, the following electrophysiological characteristics of guinea-pig AVN cells are distinct from those characteristics previously reported for the rabbit AVN: (1) an absence of transient outward current, (2) the presence of two components of delayed outward current, and (3) the presence of a Ba(2+)-sensitive inwardly rectifying current at negative voltages. The guinea-pig AVN isolated cell preparation may be valuable in providing additional insights into the cellular electrophysiology of this important region of the heart.

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Section: Comparison With Previous Studiessupporting

confidence: 68%

Section: Introductionmentioning

confidence: 98%

Characteristics of single cells isolated from the atrioventricular node of the adult guinea-pig heart.

Yuill¹,

Hancox²

2002

Pfl�gers Archiv European Journal of Physiology

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“…25 Briefly, the left atrium (LA) was dissected from the collagenase-digested heart, finely chopped, and gently shaken in enzyme, at 37°C. Tissues were re-suspended in enzyme and agitated, the supernatant centrifuged, and the cardiomyocyte pellet re-suspended in KB solution comprising (mM): KOH (70), KCl (40), l -glutamic acid (50), taurine (20), KH 2 PO 4 (20), MgCl 2 (3), glucose (10), HEPES (10), EGTA (0.5), pH 7.2 (37°C).…”

Section: Methodsmentioning

confidence: 99%

Chronic myocardial infarction promotes atrial action potential alternans, afterdepolarizations, and fibrillation

Kettlewell

Burton

Smith

et al. 2013

Cardiovascular Research

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AimsAtrial fibrillation (AF) is increased in patients with heart failure resulting from myocardial infarction (MI). We aimed to determine the effects of chronic ventricular MI in rabbits on the susceptibility to AF, and underlying atrial electrophysiological and Ca2+-handling mechanisms.Methods and resultsIn Langendorff-perfused rabbit hearts, under β-adrenergic stimulation with isoproterenol (ISO; 1 µM), 8 weeks MI decreased AF threshold, indicating increased AF susceptibility. This was associated with increased atrial action potential duration (APD)-alternans at 90% repolarization, by 147%, and no significant change in the mean APD or atrial global conduction velocity (CV; n = 6–13 non-MI hearts, 5–12 MI). In atrial isolated myocytes, also under β-stimulation, L-type Ca2+ current (ICaL) density and intracellular Ca2+-transient amplitude were decreased by MI, by 35 and 41%, respectively, and the frequency of spontaneous depolarizations (SDs) was substantially increased. MI increased atrial myocyte size and capacity, and markedly decreased transverse-tubule density. In non-MI hearts perfused with ISO, the ICaL-blocker nifedipine, at a concentration (0.02 µM) causing an equivalent ICaL reduction (35%) to that from the MI, did not affect AF susceptibility, and decreased APD.ConclusionChronic MI in rabbits remodels atrial structure, electrophysiology, and intracellular Ca2+ handling. Increased susceptibility to AF by MI, under β-adrenergic stimulation, may result from associated production of atrial APD alternans and SDs, since steady-state APD and global CV were unchanged under these conditions, and may be unrelated to the associated reduction in whole-cell ICaL. Future studies may clarify potential contributions of local conduction changes, and cellular and subcellular mechanisms of alternans, to the increased AF susceptibility.

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“…Cells from this region are also typically of a relatively small size, with cell capacitances ranging approximately between ∼ 29-40 pF [Hancox et al, 1993;Munk et al, 1996]. Additionally, cell input resistance is high (∼ 420-1,200 MΩ [Hancox et al, 1993;Munk et al, 1996;Workman et al, 2000]), which, as for the rabbit SAN, reflects a sparsity or absence of channels for the inwardly rectifying potassium current, I K1 . The absence of a functional I K1 over a voltage-range relevant to the pacemaker depolarization appears to be a key difference between pacemaking and nonpacemaking cells and makes the membrane potential highly labile over the diastolic voltage range.…”

Section: Basic Passive and Active Membrane Propertiesmentioning

confidence: 99%

Progress and Gaps in Understanding the Electrophysiological Properties of Morphologically Normal Cells From the Cardiac Atrioventricular Node

Hancox¹,

Yuill

Mitcheson

et al. 2003

Int. J. Bifurcation Chaos

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The atrioventricular node (AVN) is a small but critically important component of the cardiac electrical conduction system and is located at the junction between right atrium and right ventricle of the heart. It plays important roles in normal and abnormal impulse propagation. Mathematical models of the conduction properties of the AVN have been made, but detailed in silico reconstruction of AVN electrophysiology lags behind that of other cardiac regions. One important facet of detailed reconstruction of AVN electrical activity is the development of comprehensive, ionic conductance-based models of single cell electrophysiology. With a view to facilitating the construction of such models, this article reviews progress made regarding single AVN cell electrophysiological data during the last decade, predominantly focusing on that derived from morphologically normal AVN cells. Properties and potential roles of a range of currents are discussed: including L-type and T-type calcium currents (I Ca,L and I Ca,T respectively), background current, hyperpolarization-activated current (I f ), delayed and transient outward potassium currents (I Kr and I to , respectively), sodium-calcium exchanger current (I NaCa ), the sustained inward current (I st ) and acetylcholine-activated potassium current (I KACh ).

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Rate-dependency of Action Potential Duration and Refractoriness in Isolated Myocytes from the Rabbit AV Node and Atrium

Abstract: . (2000) Ratedependency of action potential duration and refractoriness in isolated myocytes from the rabbit AV node and atrium. Journal of Molecular and Cellular Cardiology, 32 (8

Cited by 15 publications

References 42 publications

Characteristics of single cells isolated from the atrioventricular node of the adult guinea-pig heart.

Characteristics of single cells isolated from the atrioventricular node of the adult guinea-pig heart.

Chronic myocardial infarction promotes atrial action potential alternans, afterdepolarizations, and fibrillation

Progress and Gaps in Understanding the Electrophysiological Properties of Morphologically Normal Cells From the Cardiac Atrioventricular Node

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