A hyperpolarization-activated inward current in human myocardial cells

Thüringer, Dominique; Lauribe, Philippe; Escande, Denis

doi:10.1016/0022-2828(92)91833-q

Cited by 35 publications

(23 citation statements)

References 12 publications

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“…The presence of HCN channels in diverse types of heart cells is compatible with reports describing I f currents in ventricular [42][43][44][45] and atrial myocytes [46] as well as in different conduction tissues [47]. The I f current from ventricular myocytes differs significantly from that of sinoatrial node cells in the voltage dependence of activation.…”

Section: Native Versus Cloned Cardiac Pacemaker Channelssupporting

confidence: 75%

Structure and Function of Cardiac Pacemaker Channels

Ludwig¹,

Zong²,

Hofmann³

et al. 1999

Cell Physiol Biochem

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Cardiac pacemaking is controlled by a mixed Na⁺/K⁺ current named I_f, which is activated by hyperpolarized membrane potentials. Recently, a family of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels has been cloned. The members of this family exhibit the general features of I_f channels. This review describes the molecular diversity of the HCN channel family and the structural determinants of channel function including activation by voltage, modulation by cylic nucleotides and ion permeation. The relationships beween cloned HCN channel types and native cardiac I_f currents are explored.

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Section: Native Versus Cloned Cardiac Pacemaker Channelssupporting

confidence: 75%

Structure and Function of Cardiac Pacemaker Channels

Ludwig¹,

Zong²,

Hofmann³

et al. 1999

Cell Physiol Biochem

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“…I f is present in atrial myocytes. 66,67 A role for I f in atrial ectopy has been suggested, 66 but atrial I f function has been questioned because of limited activation at atrial MDP. 67 Atrial cells have large inward I Na , 68 providing energy for rapid conduction.…”

Section: Ionic Mechanismsmentioning

confidence: 99%

Differential Distribution of Cardiac Ion Channel Expression as a Basis for Regional Specialization in Electrical Function

Schram

Pourrier

Melnyk

et al. 2002

Circulation Research

378

283

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Abstract-The cardiac electrical system is designed to ensure the appropriate rate and timing of contraction in all regions of the heart, which are essential for effective cardiac function. Well-controlled cardiac electrical activity depends on specialized properties of various components of the system, including the sinoatrial node, atria, atrioventricular node, His-Purkinje system, and ventricles. Cardiac electrical specialization was first recognized in the mid 1800s, but over the past 15 years, an enormous amount has been learned about how specialization is achieved by differential expression of cardiac ion channels. More recently, many aspects of the molecular basis have been revealed. Although the field is potentially vast, an appreciation of key elements is essential for any clinician or researcher wishing to understand modern cardiac electrophysiology. This article reviews the major regionally determined features of cardiac electrical function, discusses underlying ionic bases, and summarizes present knowledge of ion channel subunit distribution in relation to functional specialization. Key Words: ion channels Ⅲ molecular biology Ⅲ conduction Ⅲ cardiac arrhythmias Ⅲ antiarrhythmic drugs C ardiac function depends on the appropriate timing of contraction in various regions, as well as on appropriate heart rate. To subserve these functions, electrical activity in each region is adapted to its specialized function. Regionally specialized cardiac electrical function was recognized in the mid 1800s, when Stannius 1 demonstrated that ligatures in the superior vena caval sinus region of the frog caused cardiac asystole, with the sinus continuing to beat. With the widespread application to cardiac ion channel study of patchclamp methodologies in the 1980s and molecular biology in the 1990s, many underlying mechanisms have been unraveled. The present article reviews the major regionally determined features of cardiac electrical function and the present knowledge regarding ionic and molecular bases. Overview of Regional Functional SpecificityFigure 1 illustrates typical regional action potential (AP) properties in the heart. The normal cardiac impulse originates in the sinoatrial node (SAN) and propagates through the atria to reach the atrioventricular node (AVN). From the AVN, electrical activity passes rapidly through the cable-like HisPurkinje system to reach the ventricles, triggering cardiac pumping action. Figure 2 shows the ionic currents involved in a schematic cardiac AP, provides standard abbreviations for currents and their corresponding subunits, and summarizes principal localization data discussed elsewhere in the present review. Ionic and Molecular Basis of Functional Specificity Sinoatrial Node Cellular Electrophysiology and FunctionThe SAN, located in the right atrial (RA) roof between the venae cavae, 2 is specialized for physiological pacemaker function. Heart rate control is achieved through autonomic regulation of SAN pacemaking. SAN APs have a relatively positive maximum diastolic potential (MDP...

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“…However, I f is present in both automatic 1 and nonautomatic [2][3][4][5][6] regions of the heart, and the threshold voltage varies widely among cardiac regions, being least negative in sinus node (Ϫ40 mV in rabbit 7 ) and most negative in ventricle (Ϫ108 mV or more negative 5,8,9 ). Interestingly, I f activates at less negative voltages in newborn ventricle (Ϫ70 mV in rat 8,10 ).…”

mentioning

confidence: 99%

HCN2 Overexpression in Newborn and Adult Ventricular Myocytes

Barbuti

Protas

et al. 2001

Circulation Research

128

143

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Abstract-Ventricular pacemaker current (I f ) shows distinct voltage dependence as a function of age, activating outside the physiological range in normal adult ventricle, but less negatively in neonatal ventricle. However, heterologously expressed HCN2 and HCN4, the putative molecular correlates of ventricular I f , exhibit only a modest difference in activation voltage. We therefore prepared an adenoviral construct (AdHCN2) of HCN2, the dominant ventricular isoform at either age, and used it to infect neonatal and adult rat ventricular myocytes to investigate the role of maturation on current gating. The expressed current exhibited an 18-mV difference in activation (V 1/2 Ϫ95.9Ϯ1.9 in adult; Ϫ77.6Ϯ1.6 mV in neonate), comparable to the 22-mV difference between native I f in adult and neonatal cultures (V 1/2 Ϫ98.7 versus Ϫ77.0 mV). This did not result from developmental differences in basal cAMP, because saturating cAMP in the pipette caused an equivalent positive shift in both preparations. In the neonate, AdHCN2 caused a significant increase in spontaneous rate compared with control (88Ϯ5 versus 48Ϯ4 bpm). In adult, where HCN2 activates more negatively, the effect was evident only during anodal excitation, requiring significantly less stimulus energy than control (2149Ϯ266 versus 3140Ϯ279 mV ⅐ ms).

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A hyperpolarization-activated inward current in human myocardial cells

Cited by 35 publications

References 12 publications

Structure and Function of Cardiac Pacemaker Channels

Structure and Function of Cardiac Pacemaker Channels

Differential Distribution of Cardiac Ion Channel Expression as a Basis for Regional Specialization in Electrical Function

HCN2 Overexpression in Newborn and Adult Ventricular Myocytes

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