Role of acetylcholine in induction of repetitive activity in human atrial fibers

Hou, Zone‐Yuan; Lin, Chia-Cheng; Vassalle, Mario; Chiang, Benjamin N.; Cheng, Kwok-Kei

doi:10.1152/ajpheart.1989.256.1.h74

Cited by 12 publications

(16 citation statements)

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“…In the experimental paradigm used in these studies, contraction evoked by ISO was measured, followed by the simultaneous application of ISO with a muscarinic agonist in which no ISO effect was observed. After washout of the muscarinic agonist, the effect of ISO on contractility was larger than in the previous applications (19,20). This rebound effect has been consistently observed.…”

Section: Discussionsupporting

confidence: 49%

β-Adrenergic Receptor Activation Induces Internalization of Cardiac Cav1.2 Channel Complexes through a β-Arrestin 1-mediated Pathway

Lipsky

Potts

Tarzami

et al. 2008

Journal of Biological Chemistry

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Voltage-dependent calcium channels (VDCCs) play a pivotal role in normal excitation-contraction coupling in cardiac myocytes. These channels can be modulated through activation of ␤-adrenergic receptors (␤-ARs), which leads to an increase in calcium current (I Ca-L ) density through cardiac Ca v 1 channels as a result of phosphorylation by cAMP-dependent protein kinase A. Changes in I Ca-L density and kinetics in heart failure often occur in the absence of changes in Ca v 1 channel expression, arguing for the importance of posttranslational modification of these channels in heart disease. The precise molecular mechanisms that govern the regulation of VDCCs and their cell surface localization remain unknown. Our data show that sustained ␤-AR activation induces internalization of a cardiac macromolecular complex involving VDCC and ␤-arrestin 1 (␤-Arr1) into clathrincoated vesicles. Pretreatment of myocytes with pertussis toxin prevents the internalization of VDCCs, suggesting that G i/o mediates this response. A peptide that selectively disrupts the interaction between Ca V 1.2 and ␤-Arr1 and tyrosine kinase inhibitors readily prevent agonist-induced VDCC internalization. These observations suggest that VDCC trafficking is mediated by G protein switching to G i of the ␤-AR, which plays a prominent role in various cardiac pathologies associated with a hyperadrenergic state, such as hypertrophy and heart failure. Regulation of voltage-dependent calcium channels (VDCCs)3 plays a pivotal role in excitation-contraction coupling in cardiac myocytes. During the action potential upstroke, membrane depolarization causes the opening of VDCCs, encoded by the pore-forming ␣ 1 subunit, Ca v 1.2 (1). Ca 2ϩ entry through VDCCs triggers the release of Ca 2ϩ from the sarcoplasmic reticulum via ryanodine receptors. Although the regulation of VDCCs in the heart has been extensively studied, key molecular mechanisms underlying channel function, trafficking, membrane targeting, retention, and internalization remain unknown. Activation of the ␤-AR, a G protein-coupled receptor (GPCR), leads to positive inotropic effects mediated by phosphorylation of the VDCC via cAMP-dependent protein kinase A (2). This, however, is a transient phenomenon since persistent activation of the receptor causes its subsequent phosphorylation by GPCR kinases (GRKs) (3), causing the ␤-AR to become a target for arrestin (4), which mediates the recruitment of the receptor into clathrin-coated vesicles (5).In addition to decreasing single channel permeability, persistent membrane depolarization can regulate the number of Ca v 1.2 channels at the plasma membrane. For example, sustained KCl-induced depolarization of rat cortical neurons effectively decreases Ca v 1.2 channel activity (6). Ca v 1.2 channels have been proposed to contain a membrane-targeting domain within their calmodulin (CaM)-binding domain in the C terminus (7). Pitt and colleagues (8) showed that Ca 2ϩ -CaM interaction with this domain accelerated the rate of trafficking of Ca v 1.2 channels to ...

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Section: Discussionsupporting

confidence: 49%

β-Adrenergic Receptor Activation Induces Internalization of Cardiac Cav1.2 Channel Complexes through a β-Arrestin 1-mediated Pathway

Lipsky

Potts

Tarzami

et al. 2008

Journal of Biological Chemistry

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“…It is of interest that in human atrial tissues [39], acetylcholine (ACh) decreases force, AP duration and the positivity of the plateau and suppresses the activity of spontaneous fibers. However, during the recovery often there is a rebound increase in some AP parameters and in force.…”

Section: Role Of Na + In Electrical Toxicitymentioning

confidence: 99%

“…Epinephrine induces V os and aftercontractions and ACh abolished them. However, in the presence of epinephrine, during washout of ACh, V os and aftercontractions are larger, and repetitive activity is often induced [39]. The rebound effects of ACh may in part be related to the fact that ACh increases a i Na and may induce overdrive excitation [95].…”

Section: Role Of Na + In Electrical Toxicitymentioning

confidence: 99%

Calcium Overload and Cardiac Function

Vassalle

Chen

2004

J Biomed Sci

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The changes in cardiac function caused by calcium overload are reviewed. Intracellular Ca²⁺ may increase in different structures [e.g. sarcoplasmic reticulum (SR), cytoplasm and mitochondria] to an excessive level which induces electrical and mechanical abnormalities in cardiac tissues. The electrical manifestations of Ca²⁺ overload include arrhythmias caused by oscillatory (V_os) and non-oscillatory (V_ex) potentials. The mechanical manifestations include a decrease in force of contraction, contracture and aftercontractions. The underlying mechanisms involve a role of Na⁺ in electrical abnormalities as a charge carrier in the Na⁺-Ca²⁺ exchange and a role of Ca²⁺ in mechanical toxicity. Ca²⁺ overload may be induced by an increase in [Na⁺]_i through the inhibition of the Na⁺-K⁺ pump (e.g. toxic concentrations of digitalis) or by an increase in Ca²⁺ load (e.g. catecholamines). The Ca²⁺ overload is enhanced by fast rates. Purkinje fibers are more susceptible to Ca²⁺ overload than myocardial fibers, possibly because of their greater Na⁺ load. If the SR is predominantly Ca²⁺ overloaded, V_os and fast discharge are induced through an oscillatory release of Ca²⁺ in diastole from the SR; if the cytoplasm is Ca²⁺ overloaded, the non-oscillatory V_ex tail is induced at negative potentials. The decrease in contractile force by Ca²⁺ overload appears to be associated with a decrease in high energy phosphates, since it is enhanced by metabolic inhibitors and reduced by metabolic substrates. The ionic currents I_os and I_ex underlie V_os and V_ex, respectively, both being due to an electrogenic extrusion of Ca²⁺ through the Na⁺-Ca²⁺ exchange. I_os is an oscillatory current due to an oscillatory release of Ca²⁺ in early diastole from the Ca²⁺-overloaded SR, and I_ex is a non-oscillatory current due to the extrusion of Ca²⁺ from the Ca²⁺-overloaded cytoplasm. I_os and I_ex can be present singly or simultaneously. An increase in [Ca²⁺]_i appears to be involved in the short- and long-term compensatory mechanisms that tend to maintain cardiac output in physiological and pathological conditions. Eventually, [Ca²⁺]_i may increase to overload levels and contribute to cardiac failure. Experimental evidence suggests that clinical concentrations of digitalis increase force in Ca²⁺-overloaded cardiac cells by decreasing the inhibition of the Na⁺-K⁺ pump by Ca²⁺, thereby leading to a reduction in Ca²⁺ overload and to an increase in force of contraction.

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“…It is generally believed that mammalian including human heart muscles do not generate tetanic contraction [17], in contrast to fast-contracting skeletal muscles [4], because of the rather low APD and refractory period comparable to that of twitch duration. However, heart muscle cells of small rodents such as hamster have prominent transient outward K + currents and very short APD 50 [25], and they may be an exception to this general rule.…”

Section: Tetanic Contraction In Isolated Hamster Atriamentioning

confidence: 99%

Reentrant Tachyarrhythmias in Right Atria of Cardiomyopathic versus Healthy Syrian Hamster

et al. 1999

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We studied the role of acetylcholine (ACh) and calcium overload in the induction of atrial flutter or atrial fibrillation (AF) in right atria from 34 normal male Syrian hamsters (F1B) and 33 cardiomyopathic Syrian hamsters (BIO 14.6) associated with focal myocardial necrosis. Action potential (AP) was recorded with conventional microelectrode techniques and twitch force by a transducer. ACh (0.1, 1 and 10 μM) induced high-frequency AF (around 33 Hz) along with tension oscillations and contracture in 7 of 12 normal hamster atria. These effects of ACh were abolished by tetrodotoxin or quinidine as well as by atropine. In contrast, ACh induced AF only in 1 of 12 myopathic atria. In both normal and myopathic atria, ACh induced similar changes in AP duration, spontaneous rate and force. The effects of calcium overload were tested by means of a high [Ca²⁺]_o (8.1 mM) low [K⁺]_o (1 mM) solution in another series of experiments. This solution also induced incidence of AF higher in normal (10/12) than in myopathic atria (4/12). The calcium load was also increased by high-frequency pacing (32 Hz for 3 or 30 s): AF occurred in normal atria (5/8), but not in myopathic atria (0/8). Measurement of the refractory period revealed a longer refractory period in myopathic than in control atria. We concluded that the lower incidence of AF in myopathic atria was probably due to their longer refractory period and the associated focal myocardial necrosis which then hindered the establishment of such a reentrant rhythm.

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Role of acetylcholine in induction of repetitive activity in human atrial fibers

Cited by 12 publications

References 0 publications

β-Adrenergic Receptor Activation Induces Internalization of Cardiac Cav1.2 Channel Complexes through a β-Arrestin 1-mediated Pathway

β-Adrenergic Receptor Activation Induces Internalization of Cardiac Cav1.2 Channel Complexes through a β-Arrestin 1-mediated Pathway

Calcium Overload and Cardiac Function

Reentrant Tachyarrhythmias in Right Atria of Cardiomyopathic versus Healthy Syrian Hamster

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