Facilitation of the L-type calcium current in rabbit sino-atrial cells: effect on cardiac automaticity

Mangoni, Matteo E.; Fontanaud, Pierre; Noble, Penelope J.; Noble, Denis; Benkemoun, Henri; Nargeot, Joël; Richard, Sylvain

doi:10.1016/s0008-6363(00)00182-6

Cited by 30 publications

(27 citation statements)

References 48 publications

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“…Both I Na and I CaT have low voltage activation thresholds and, therefore, strongly amplified the initial cAMP-sensitive signaling of I f -induced early depolarization in the 1999 Demir et al model (6). However, I CaT was later found to be relatively small and detected only in 20% of rabbit SANCs (38); I Na is negligible in primary/central rabbit SANCs (initiating excitations in the sinoatrial node). Furthermore, being cAMP/PKA independent, I CaT cannot control late DD and the pacemaker rate.…”

Section: Comparisons With Other Sanc Modelsmentioning

confidence: 98%

“…A critical parameter determining the ICaL contribution to DD is its activation threshold, and, therefore, this parameter was carefully considered in our model. The activation threshold has been measured in several patch-clamp studies of isolated rabbit SANCs and was found to be "positive to Ϫ45 to Ϫ50 mV" (8), "around Ϫ60 mV" (48), "between Ϫ50 and Ϫ40 mV" (38), or "approximately Ϫ40 mV" (52). A relatively low activation threshold of I CaL in SANCs might be explained, at least in part, by two factors: 1) L-type Ca 2ϩ channels could be phosphorylated by PKA, which is highly active in the basal state (43,50); and 2) ICaL in SANCs might be a combination of Cav1.2 and Cav1.3, as shown in mouse SANCs (37).…”

Section: Simulation Of I Cal In the Basal Statementioning

confidence: 99%

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A novel quantitative explanation for the autonomic modulation of cardiac pacemaker cell automaticity via a dynamic system of sarcolemmal and intracellular proteins

Maltsev

Lakatta

2010

American Journal of Physiology-Heart and Circulatory Physiology

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Classical numerical models have attributed the regulation of normal cardiac automaticity in sinoatrial node cells (SANCs) largely to G protein-coupled receptor (GPCR) modulation of sarcolemmal ion currents. More recent experimental evidence, however, has indicated that GPCR modulation of SANCs automaticity involves spontaneous, rhythmic, local Ca(2+) releases (LCRs) from the sarcoplasmic reticulum (SR). We explored the GPCR rate modulation of SANCs using a unique and novel numerical model of SANCs in which Ca(2+)-release characteristics are graded by variations in the SR Ca(2+) pumping capability, mimicking the modulation by phospholamban regulated by cAMP-mediated, PKA-activated signaling. The model faithfully predicted the entire range of physiological chronotropic modulation of SANCs by the activation of beta-adrenergic receptors or cholinergic receptors only when experimentally documented changes of sarcolemmal ion channels are combined with a simultaneous increase/decrease in SR Ca(2+) pumping capability. The novel numerical mechanism of GPCR rate modulation is based on numerous complex synergistic interactions between sarcolemmal and intracellular processes via membrane voltage and Ca(2+). Major interactions include changes of diastolic Na(+)/Ca(2+) exchanger current that couple earlier/later diastolic Ca(2+) releases (predicting the experimentally defined LCR period shift) of increased/decreased amplitude (predicting changes in LCR signal mass, i.e., the product of LCR spatial size, amplitude, and number per cycle) to the diastolic depolarization and ultimately to the spontaneous action potential firing rate. Concomitantly, larger/smaller and more/less frequent activation of L-type Ca(2+) current shifts the cellular Ca(2+) balance to support the respective Ca(2+) cycling changes. In conclusion, our model simulations corroborate recent experimental results in rabbit SANCs pointing to a new paradigm for GPCR heart rate modulation by a complex system of dynamically coupled sarcolemmal and intracellular proteins.

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Section: Comparisons With Other Sanc Modelsmentioning

confidence: 98%

Section: Simulation Of I Cal In the Basal Statementioning

confidence: 99%

A novel quantitative explanation for the autonomic modulation of cardiac pacemaker cell automaticity via a dynamic system of sarcolemmal and intracellular proteins

Maltsev

Lakatta

2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…The inactivation of ICa,L consists of two exponential terms: rapid and slow components. The rapid component is mediated by the intracellular Ca 2ϩ -dependent inactivation with a time constant ranging from 10 to 30 ms for rabbit SA node cells, whereas the slower component reflects the voltage-dependent inactivation with a time constant of 30ϳ70 ms (5,34,72,81,102). To describe the inactivation process, we adopted a simple model in which the Ca 2ϩ -dependent inactivation process is independent of the voltage-dependent one (see Refs.…”

Section: Model Developmentmentioning

confidence: 99%

Dynamical description of sinoatrial node pacemaking: improved mathematical model for primary pacemaker cell

Kurata

Hisatome

Imanishi

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

166

293

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We developed an improved mathematical model for a single primary pacemaker cell of the rabbit sinoatrial node. Original features of our model include 1) incorporation of the sustained inward current (I(st)) recently identified in primary pacemaker cells, 2) reformulation of voltage- and Ca(2+)-dependent inactivation of the L-type Ca(2+) channel current (I(Ca,L)), 3) new expressions for activation kinetics of the rapidly activating delayed rectifier K(+) channel current (I(Kr)), and 4) incorporation of the subsarcolemmal space as a diffusion barrier for Ca(2+). We compared the simulated dynamics of our model with those of previous models, as well as with experimental data, and examined whether the models could accurately simulate the effects of modulating sarcolemmal ionic currents or intracellular Ca(2+) dynamics on pacemaker activity. Our model represents significant improvements over the previous models, because it can 1) simulate whole cell voltage-clamp data for I(Ca,L), I(Kr), and I(st); 2) reproduce the waveshapes of spontaneous action potentials and ionic currents during action potential clamp recordings; and 3) mimic the effects of channel blockers or Ca(2+) buffers on pacemaker activity more accurately than the previous models.

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“…Modest depolarization induces an increase in I Ca amplitude and a slowing of I Ca inactivation, which was blocked by ryanodine, suggesting a role for sarcoplasmic reticulum Ca release (Barrere-Lemaire et al, Brette et al, 2003a). The mechanism and physiological role of this facilitation is not elucidated yet, although it has been suggested that it can regulate cardiac automaticity in sinoatrial node cells (Mangoni et al, 2000).…”

Section: Facilitationmentioning

confidence: 99%

Ca2+ currents in cardiac myocytes: Old story, new insights

Brette

Leroy

Guennec

et al. 2006

Progress in Biophysics and Molecular Biology

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Facilitation of the L-type calcium current in rabbit sino-atrial cells: effect on cardiac automaticity

Abstract: Facilitation of I(Ca,L) is present in rabbit sino-atrial cells. The underlying mechanism reflects modulation of I(Ca,L) decay kinetics by diastolic membrane potential and frequency of depolarization. This phenomenon may provide an important regulatory mechanism of sino-atrial automaticity.

Cited by 30 publications

References 48 publications

A novel quantitative explanation for the autonomic modulation of cardiac pacemaker cell automaticity via a dynamic system of sarcolemmal and intracellular proteins

A novel quantitative explanation for the autonomic modulation of cardiac pacemaker cell automaticity via a dynamic system of sarcolemmal and intracellular proteins

Dynamical description of sinoatrial node pacemaking: improved mathematical model for primary pacemaker cell

Ca2+ currents in cardiac myocytes: Old story, new insights

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