Early Down‐Regulation of K<sup>+</sup> Channel Genes and Currents in the Postinfarction Heart

Huang, Biao; Qin, DAYl; El‐Sherif, Nabil

doi:10.1046/j.1540-8167.2000.01252.x

Cited by 58 publications

(51 citation statements)

References 31 publications

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“…This procedure eliminates artifacts due to ischemia or apoptosis and thus, deals with reactive hypertrophy. 24 After LV infarction, RV hypertrophy, an important determinant in the prognosis of heart failure, 25 is also observed 26,27 and might be independent of mechanical factors. 28 One week after surgery, V C ( Figure 1A) and C m (see below) were similar in myocytes isolated from post-MI and shamoperated rats, indicating that cellular hypertrophy had not occurred at this stage.…”

Section: Ionic Channel Remodeling Precedes Cellular Hypertrophy After MImentioning

confidence: 99%

Mineralocorticoid Receptor Antagonism Prevents the Electrical Remodeling That Precedes Cellular Hypertrophy After Myocardial Infarction

et al. 2004

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Background-Cardiac hypertrophy underlies arrhythmias and sudden death, for which mineralocorticoid receptor (MR) activity has recently been implicated. We sought to establish the sequence of ionic events that link the initiating insult and MR to hypertrophy development. Methods and Results-Using whole-cell, patch-clamp and quantitative reverse transcription-polymerase chain reaction techniques on right ventricular myocytes of a myocardial infarction (MI) rat model, we examined the cellular response over time. One week after MI, no sign of cellular hypertrophy was found, but action potential duration (APD) was lengthened. Both an increase in Ca 2ϩ current (I Ca ) and a decrease in K ϩ transient outward current (I to ) underlay this effect. Consistently, the relative expression of mRNA coding for the Ca 2ϩ channel ␣1C subunit (Ca v 1.2) increased, and that of the K ϩ channel K v 4.2 subunit decreased. Three weeks after MI, AP prolongation endured, whereas cellular hypertrophy developed. I Ca density, Ca v 1.2, and K v 4.2 mRNA levels regained control levels, but I to density remained reduced. Long-term treatment with RU28318, an MR antagonist, prevented this electrical remodeling. In a different etiologic model of abdominal aortic constriction, we confirmed that APD prolongation and modifications of ionic currents precede cellular hypertrophy. Conclusions-Electrical remodeling, which is triggered at least in part by MR activation, is an initial, early cellular response to hypertrophic insults.

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Section: Ionic Channel Remodeling Precedes Cellular Hypertrophy After MImentioning

confidence: 99%

Mineralocorticoid Receptor Antagonism Prevents the Electrical Remodeling That Precedes Cellular Hypertrophy After Myocardial Infarction

et al. 2004

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“…Specifically, an increase in L-type Ca current density and decrease in potassium current densities are observed in heart failure. [53][54][55] I Ks and I Kr are also responsible for the increased sudden cardiac death seen in LQT1 and LQT2. Furthermore, epinephrine may induce torsade, whereas left sympathectomy and β-blockers are antiarrhythmic in LQT1.…”

Section: Myocardial Infarction Heart Failure and Sympathetic Innervmentioning

confidence: 99%

The Role of the Autonomic Nervous System in Sudden Cardiac Death

Vaseghi

Shivkumar²

2008

Progress in Cardiovascular Diseases

328

242

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The cardiac autonomic nervous system consists of 2 branches-the sympathetic and the parasympathetic systems-that work in a delicately tuned, yet opposing fashion in the heart. This extrinsic control mechanism can dominate intrinsic regulatory mechanisms that modulate heart rate and cardiac output. These branches differ in their neurotransmitters (norepinephrine and acetylcholine) and exert stimulatory or inhibitory effects on target tissue via adrenergic and muscarinic receptors. Stimulation of the sympathetic branch exerts facilitatory effects on function, increasing heart rate and myocardial contractility, whereas the stimulation of the parasympathetic branch exerts inhibitory effects that decrease heart rate and contractility. The interplay between these two branches is complex and susceptible to control at several levels, from centrally mediated baroreceptors and chemoreceptors to local interneuronal interactions.Alterations in autonomic function occur in several interrelated cardiac conditions including sudden cardiac death, congestive heart failure, diabetic neuropathy, and myocardial ischemia. Although the full extent of these changes has not been elucidated, multiple autonomic remodeling mechanisms have been observed at both the neuronal fiber and myocardial cellular level that contribute to an arrhythmogenic substrate. We describe the anatomy of both systems in this review. However, the review will premdominantly focus on the sympathetic system, whose role in the modulation of cardiac arrhythmias is slightly better delineated. Cardiac Autonomic Innervation: NeuroanatomyBoth branches of the autonomic nervous system are composed of both afferent and efferent as well interneuronal fibers (Fig 1). Sympathetic innervation originates mainly in the right and left stellate ganglia. These fibers travel along the epicardial vascular structures of the heart and penetrate into the underlying myocardium similar to coronary vessels and end as sympathetic nerve terminals reaching the endocardium. Based on norepinephrine content studies, a gradient exists in sympathetic innervation from atria to the ventricles and from base to apex of the heart. Therefore, the atria are most densely innervated, but the ventricles are also supplied with a sympathetic network, most densely at the base. 1 Parasympathetic effects are carried by the right and left vagus nerves, originating in the medulla. The vagus nerve further divides into the superior and inferior cardiac nerves, finally merging with the postganglionic sympathetic neurons to form a plexus of nerves at the base of the heart, known as the cardiac plexus. In contrast to sympathetic neurons, after parasympathetic fibers cross the atrioventricular (AV) groove along the surface of the heart,

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“…Three days after coronary occlusion, reduction of potassium currents (I k , I to and I k1 ) can be observed in the left ventricle, showing differences between endocardial and epicardial layers (59,60). Moreover, the expression of some subunits of potassium channels remains reduced in infarcted rats, which affects the repolarization process.…”

Section: Electrophysiological Changes and Arrhythmogenesismentioning

confidence: 99%

“…Because this process is not homogeneous among all myocardium that survive infarction (57), the repolarization process can become asynchronous in different parts of the left ventricle, increasing susceptibility to development of ventricular arrhythmias (59). These early alterations are dissociated from structural remodeling and help to explain the enhanced duration of action potentials observed in myocytes early after infarction (60). Although the most common mechanisms underlying ventricular arrhythmias are the re-entrant circuits, a non-reentrant mechanism can also lead to electrical instability in the myocardium.…”

Section: Electrophysiological Changes and Arrhythmogenesismentioning

confidence: 99%

Remodeling in the ischemic heart: the stepwise progression for heart

Mill¹,

Stefanon

Santos

et al. 2011

Braz J Med Biol Res

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Coronary artery disease is the leading cause of death in the developed world and in developing countries. Acute mortality from acute myocardial infarction (MI) has decreased in the last decades. However, the incidence of heart failure (HF) in patients with healed infarcted areas is increasing. Therefore, HF prevention is a major challenge to the health system in order to reduce healthcare costs and to provide a better quality of life. Animal models of ischemia and infarction have been essential in providing precise information regarding cardiac remodeling. Several of these changes are maladaptive, and they progressively lead to ventricular dilatation and predispose to the development of arrhythmias, HF and death. These events depend on cell death due to necrosis and apoptosis and on activation of the inflammatory response soon after MI. Systemic and local neurohumoral activation has also been associated with maladaptive cardiac remodeling, predisposing to HF. In this review, we provide a timely description of the cardiovascular alterations that occur after MI at the cellular, neurohumoral and electrical level and discuss the repercussions of these alterations on electrical, mechanical and structural dysfunction of the heart. We also identify several areas where insufficient knowledge limits the adoption of better strategies to prevent HF development in chronically infarcted individuals.

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Early Down‐Regulation of K⁺ Channel Genes and Currents in the Postinfarction Heart

Cited by 58 publications

References 31 publications

Mineralocorticoid Receptor Antagonism Prevents the Electrical Remodeling That Precedes Cellular Hypertrophy After Myocardial Infarction

Mineralocorticoid Receptor Antagonism Prevents the Electrical Remodeling That Precedes Cellular Hypertrophy After Myocardial Infarction

The Role of the Autonomic Nervous System in Sudden Cardiac Death

Remodeling in the ischemic heart: the stepwise progression for heart

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Early Down‐Regulation of K+ Channel Genes and Currents in the Postinfarction Heart

Cited by 58 publications

References 31 publications

Mineralocorticoid Receptor Antagonism Prevents the Electrical Remodeling That Precedes Cellular Hypertrophy After Myocardial Infarction

Mineralocorticoid Receptor Antagonism Prevents the Electrical Remodeling That Precedes Cellular Hypertrophy After Myocardial Infarction

The Role of the Autonomic Nervous System in Sudden Cardiac Death

Remodeling in the ischemic heart: the stepwise progression for heart

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Product

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Early Down‐Regulation of K⁺ Channel Genes and Currents in the Postinfarction Heart