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

Brette, Fabien; Leroy, Jérôme; Guennec, J.-Y. Le; Sallé, Laurent

doi:10.1016/j.pbiomolbio.2005.01.001

Cited by 50 publications

(43 citation statements)

References 626 publications

(652 reference statements)

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“…Among several regulatory pathways that control cardiac Ca 2+ channel activity, the best described is the β-adrenergic stimulation of I Ca,L , which contributes to the positive inotropic and part of the positive chronotropic effects of catecholamines (1,2). Although to date, 3 types of β-adrenergic receptors (β-ARs) have been cloned, β 1 -, β 2 -, and β 3 -ARs, respectively, the effect of catecholamines in human heart is generally attributed to β 1 - and β 2 -ARs, with opposite effects on hypertrophy (3,4) and apoptosis (5,6) and with a respective contribution of each receptor subtype that varies significantly depending on the cardiac tissue, the pathophysiological state, the age, or the developmental stage (7).…”

Section: Introductionmentioning

confidence: 99%

β3-adrenergic receptor activation increases human atrial tissue contractility and stimulates the L-type Ca2+ current

Skeberdis¹,

Gendviliene²,

Zablockaitė³

et al. 2008

J. Clin. Invest.

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β 3 -adrenergic receptor (β 3 -AR) activation produces a negative inotropic effect in human ventricles. Here we explored the role of β 3 -AR in the human atrium. Unexpectedly, β 3 -AR activation increased human atrial tissue contractility and stimulated the L-type Ca 2+ channel current (I Ca,L ) in isolated human atrial myocytes (HAMs). Right atrial tissue specimens were obtained from 57 patients undergoing heart surgery for congenital defects, coronary artery diseases, valve replacement, or heart transplantation. The I Ca,L and isometric contraction were recorded using a whole-cell patch-clamp technique and a mechanoelectrical force transducer. Two selective β 3 -AR agonists, SR58611 and BRL37344, and a β 3 -AR partial agonist, CGP12177, stimulated I Ca,L in HAMs with nanomolar potency and a 60%-90% efficacy compared with isoprenaline. The β 3 -AR agonists also increased contractility but with a much lower efficacy (~10%) than isoprenaline. The β 3 -AR antagonist L-748,337, β 1 -/β 2 -AR antagonist nadolol, and β 1 -/β 2 -/β 3 -AR antagonist bupranolol were used to confirm the involvement of β 3 -ARs (and not β 1 -/β 2 -ARs) in these effects. The β 3 -AR effects involved the cAMP/PKA pathway, since the PKA inhibitor H89 blocked I Ca,L stimulation and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) strongly increased the positive inotropic effect. Therefore, unlike in ventricular tissue, β 3 -ARs are positively coupled to L-type Ca 2+ channels and contractility in human atrial tissues through a cAMP-dependent pathway.

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Section: Introductionmentioning

confidence: 99%

β3-adrenergic receptor activation increases human atrial tissue contractility and stimulates the L-type Ca2+ current

Skeberdis¹,

Gendviliene²,

Zablockaitė³

et al. 2008

J. Clin. Invest.

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“…Local changes in the stress-strain loop may lead to changes in angiotensin II release and eventually affect I Ca,L and calcium homeostasis. 7,48,58 In our model, reduction of g to leads to disappearance of the notch in the action potential as well as a reduced APD (Fig. 2).…”

Section: What Triggers Electrical Remodeling?mentioning

confidence: 64%

“…Thus, the increase in APD observed in experiments cannot be reproduced by increasing g Ca,L alone. Since no changes in peak I Ca,L current size have been observed in experiments after ventricular pacing, 7,27,49 also scaling g Ca,L is not considered further. In Table 2 In Fig.…”

Section: Isosarcometric Contractionmentioning

confidence: 99%

“…In contrast, no evidence for ''atrial memory'' has been found in the goat. 69 Experimental results indicate that both the transient outward potassium (K + ) current (I to ) 57 and the L-type calcium (Ca 2+ ) current (I Ca,L ) 7,49 are involved in electrical remodeling after changing the activation sequence in the ventricles. Yu et al 72 observed a reduction in I to current size, which explains disappearance of the notch in the AP after remodeling.…”

Section: Introductionmentioning

confidence: 99%

“…These observations indicate that changes in the I Ca,L current are related to modifications in the transcription of the I Ca,L channel. 7 At present, it is unclear what mechanism drives electrical remodeling after changing the activation sequence. Based on experimental observations, Jeyaraj et al 26 suggest mechanoelectric feedback as a mechanism for electrical remodeling.…”

Section: Introductionmentioning

confidence: 99%

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Mechanoelectric Feedback as a Trigger Mechanism for Cardiac Electrical Remodeling: A Model Study

et al. 2008

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Abstract-Regional variation in ionic membrane currents causes differences in action potential duration (APD) and is proarrhythmic. After several weeks of ventricular pacing, AP morphology and duration are changed due to electrical remodeling of the transient outward potassium current (I to ) and the L-type calcium current (I Ca,L ). It is not clear what mechanism drives electrical remodeling. By modeling the cardiac muscle as a string of segments that are electrically and mechanically coupled, we investigate the hypothesis that electrical remodeling is triggered by changes in mechanical load. Contractile force generated by the sarcomeres depends on the calcium transient and on the sarcomere length. Stroke work is determined for each segment by simulating the cardiac cycle. Electrical remodeling is simulated by adapting I Ca,L kinetics such that a homogeneous distribution of stroke work is obtained. With electrical remodeling, a more homogeneous shortening of the fiber is obtained, while heterogeneity in APD increases and the repolarization wave reverses. Our results are in agreement with experimentally observed homogeneity in mechanics and heterogeneity in electrophysiology. In conclusion, electrical remodeling is a possible mechanism to reduce heterogeneity in cardiomechanics induced by ventricular pacing.

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Pharmacoresistant Ca_v2·3 (E‐type/R‐type) voltage‐gated calcium channels influence heart rate dynamics and may contribute to cardiac impulse conduction

Galetin

Tevoufouet

Sandmeyer

et al. 2012

Cell Biochemistry & Function

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Voltage-gated Ca(2+) channels regulate cardiac automaticity, rhythmicity and excitation-contraction coupling. Whereas L-type (Cav 1·2, Cav 1·3) and T-type (Cav 3·1, Cav 3·2) channels are widely accepted for their functional relevance in the heart, the role of Cav 2·3 Ca(2+) channels expressing R-type currents remains to be elucidated. We have investigated heart rate dynamics in control and Cav 2·3-deficient mice using implantable electrocardiogram radiotelemetry and pharmacological injection experiments. Autonomic block revealed that the intrinsic heart rate does not differ between both genotypes. Systemic administration of isoproterenol resulted in a significant reduction in interbeat interval in both genotypes. It remained unaffected after administering propranolol in Cav 2·3(-|-) mice. Heart rate from isolated hearts as well as atrioventricular conduction for both genotypes differed significantly. Additionally, we identified and analysed the developmental expression of two splice variants, i.e. Cav 2·3c and Cav 2·3e. Using patch clamp technology, R-type currents could be detected in isolated prenatal cardiomyocytes and be related to R-type Ca(2+) channels. Our results indicate that on the systemic level, the pharmacologically inducible heart rate range and heart rate reserve are impaired in Cav 2·3 (-|-) mice. In addition, experiments on Langendorff perfused hearts elucidate differences in basic properties between both genotypes. Thus, Cav 2·3 does not only contribute to the cardiac autonomous nervous system but also to intrinsic rhythm propagation.

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

Cited by 50 publications

References 626 publications

β3-adrenergic receptor activation increases human atrial tissue contractility and stimulates the L-type Ca2+ current

β3-adrenergic receptor activation increases human atrial tissue contractility and stimulates the L-type Ca2+ current

Mechanoelectric Feedback as a Trigger Mechanism for Cardiac Electrical Remodeling: A Model Study

Pharmacoresistant Ca_v2·3 (E‐type/R‐type) voltage‐gated calcium channels influence heart rate dynamics and may contribute to cardiac impulse conduction

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

Cited by 50 publications

References 626 publications

β3-adrenergic receptor activation increases human atrial tissue contractility and stimulates the L-type Ca2+ current

β3-adrenergic receptor activation increases human atrial tissue contractility and stimulates the L-type Ca2+ current

Mechanoelectric Feedback as a Trigger Mechanism for Cardiac Electrical Remodeling: A Model Study

Pharmacoresistant Cav2·3 (E‐type/R‐type) voltage‐gated calcium channels influence heart rate dynamics and may contribute to cardiac impulse conduction

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Product

Resources

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Pharmacoresistant Ca_v2·3 (E‐type/R‐type) voltage‐gated calcium channels influence heart rate dynamics and may contribute to cardiac impulse conduction