Leucine/isoleucine zipper coordination of ion channel macromolecular signaling complexes in the heart. Roles in inherited arrhythmias.
The sympathetic nervous system controls the force and rate of contraction of the heart. The rapid response to stress and exercise mediated by increased sympathetic nervous system (SNS) activity requires the coordinated regulation of several ion channels in response to activation of beta-adrenergic receptors. The microenvironment of target channels is mediated by the assembly of macromolecular signaling complexes in which targeting proteins recruit phosphatases and kinases and in turn bind directly to the channel protein via highly conserved leucine/isoleucine zippers (LIZs). Disruption of local signaling by disease-associated LIZ mutations unbalances the physiologic response to SNS stimulation and increases the risk of arrhythmia in mutation carriers.
Kass
R S
RS
Department of Pharmacology (Division of Cardiology), College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA. rsk20@columbia.edu
Kurokawa
J
J
Marx
S O
SO
Marks
A R
AR
D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000503:physiopathology; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D007532:Isoleucine / Q000235:genetics / Q000502:physiology*; D016350:Leucine Zippers / Q000235:genetics / Q000502:physiology*; D046911:Macromolecular Substances; D009200:Myocardial Contraction / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013564:Sympathetic Nervous System / Q000503:physiopathology
D007473:Ion Channels; D046911:Macromolecular Substances; D011943:Receptors, Adrenergic, beta; D007532:Isoleucine