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(Circulation Research. 2002;90:14.)
© 2002 American Heart Association, Inc.

Editorials

Calcium and Cardiac Rhythms

Physiological and Pathophysiological

Donald M. Bers

From the Department of Physiology, Loyola University Chicago, Stritch School of Medicine, Maywood, Ill.

Correspondence to Donald M. Bers, Department of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 S First Ave, Maywood, IL 60153. E-mail dbers@lumc.edu

Key Words: cardiac electrophysiology • pacemaker • arrhythmias • sarcoplasmic reticulum Na⁺-Ca²⁺ exchange • excitation-contraction coupling

Calcium plays two pivotal roles in cardiac excitation-contraction (E-C) coupling.¹ Ca²⁺ drives myofilament activation and carries or regulates ionic currents that are responsible for normal electrical rhythms² as well as life-threatening arrhythmias.³ In this editorial, I will focus on Ca²⁺ and pacemaker activity and arrhythmogenesis.

Ca²⁺ entry via Ca²⁺ current (I_Ca) triggers sarcoplasmic reticulum (SR) Ca²⁺ release via ryanodine receptors (RyRs), and relaxation is driven by Ca²⁺ transport by the SR Ca²⁺-ATPase and Na⁺-Ca²⁺ exchange. Two I_Ca types occur in cardiac myocytes: L-type (I_Ca,L) activated at E_m>-40 mV and T-type (I_Ca,T) activated at E_m>-60 mV (near the pacemaker range). Inward I_Ca,T and I_Ca,L can contribute importantly to both normal and abnormal cardiac depolarization. I_Ca,L is crucial in E-C coupling in all cardiac myocytes. I_Ca,T is absent in most ventricular myocytes but is present in neonatal ventricular myocytes, some atrial myocytes, and in conducting and pacemaker cells. ß-Adrenergic receptors (ß-ARs) and cAMP-dependent protein kinase (PKA) increase I_Ca,L amplitude and shift activation to more negative E_m (closer to the pacemaker range). Parasympathetic stimulation of the heart (via muscarinic receptors) can offset the ß-AR effect. Withdrawal of muscarinic activation can also cause a rebound overshoot in I_Ca,L and may contribute directly to postvagal tachycardia.^4,5 I_Ca,L is rapidly inactivated by local [Ca²⁺] at the inner channel mouth (mediated by calmodulin associated with the channel).^6,7 As [Ca²⁺]_i declines, I_Ca,L can recover partially from inactivation, even at depolarized E_m.⁸ This can allow I_Ca,L . . . [Full Text of this Article]

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