Frontiers in Myocardia

Volume: 1

Cellular Electrophysiological Mechanisms in Septic Cardiomyopathy

Author(s): Brigitte Pelzmann, Susanne Scheruebel and Klaus Zorn-Pauly

Pp: 57-84 (28)

DOI: 10.2174/9781681080604115010007

Abstract

Excitability and contractility of the heart rely on proper functioning of cardiac ion channels. Ion channels are transmembrane proteins enabling ions to cross the cell membrane and thereby changing membrane potential. Multiple studies have shown that remodelling of ion channel function occurs in various heart diseases (e.g. atrial fibrillation, heart failure) and there is growing evidence that alterations in ion channel activity play an important role in septic cardiomyopathy. The purpose of this chapter is to review sepsis-induced ion channel dysfunction. Particular emphasis is placed on the L-type calcium and the pacemaker channel. The L-type calcium channel is a key nexus linking cellular excitation and contraction and sepsis-induced channel impairment very likely contributes to the pathogenesis of myocardial depression. A reduction of heart rate variability is a further characteristic of cardiac dysfunction in sepsis probably attributable to autonomic dysfunction and/or a reduced responsiveness of the sinus node to autonomic stimuli. The pacemaker channel comprises an important final common pathway for autonomic heart rate regulation and is directly impaired by endotoxin. These facts strongly imply a major contribution of the pacemaker channel to the sepsis-induced reduction of heart rate variability.


Keywords: Action potential, Autonomic nervous system, Beat-to-beat variability, Ca2+ homeostasis, Heart rate, Heart-rate variability, Ion channels, Ivabradine, LPS, L-type calcium current ICa, L, Myocardial depression, Na+/Ca2+-exchanger INCX, Na+/K+-ATPase, Pacemaker current If, Patch-clamp, Sepsis, Sinoatrial pacemaking.

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