Cellular Electrophysiological Mechanisms in Septic Cardiomyopathy
Pp. 57-84 (28)
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.
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.