Cardiac ion channels

Abstract

Ion channels are critical for all aspects of cardiac function, including rhythmicity and contractility. Consequently, ion channels are key targets for therapeutics aimed at cardiac pathophysiologies such as atrial fibrillation or angina. At the same time, off-target interactions of drugs with cardiac ion channels can be the cause of unwanted side effects. This manuscript aims to review the physiology and pharmacology of key cardiac ion channels. The intent is to highlight recent developments for therapeutic development, as well as elucidate potential mechanisms for drug-induced cardiac side effects, rather than present an in-depth review of each channel subtype.

Association Between QT-Interval Components and Sudden Cardiac Death

“…1-3 Although the QT interval is traditionally used as a marker of ventricular repolarization, it encompasses phases 0-3 of the ventricular cardiac action potential, and involves both depolarizing and repolarizing currents. 4, 5 Even within the repolarization components of the QT interval, regional differences in electrophysiological properties (e.g., repolarization heterogeneity) and prognostic significance have been reported. 6 Accordingly, the precise component within the QT interval that is associated with SCD remains unclear.…”

Radiologic diagnosis of a type-III pleuropulmonary blastoma

“…In the largest series of PPB published, 5-year survival rates were 83% for type I PPB and 42% for type II and type III PPB (3). Pleural and mediastinal involvement at diagnosis are indicative of a poor prognosis, as does extra-pleural involvement (7,8). The most frequent sites of metastasis are the central nervous system, bone, bone marrow and the liver, and metastasis occurs in aggressive forms of PPB: Types II and III PPB.…”

Potassium channels in the sinoatrial node and their role in heart rate control

“…Ca v 1.2 is the classic L-type channel present throughout the heart that is responsible for calcium entry promoting calcium-induced calcium release from the sarcoplasmic reticulum and in the SA node is responsible for some of the action potential depolarization [7]. In contrast, Ca v 1.3 activates at more hyperpolarised potentials and contributes to pacemaking [8,9]. Sodium currents are less obvious as the main driver of depolarization.…”

“…In ventricular cells this is known as I K1 and is accounted for by members of the Kir2.0 family of inward rectifiers [9,27,28]. In contrast in the SAN and atrial cells the current is less strongly inwardly-rectifying but is characteristically increased by muscarinic agonists such as acetylcholine and carbachol (“I KACh ”) [29].…”

“…The major repolarising currents in ventricular myocytes are I Kr and I Ks and both components are also present in SAN myocytes [9,61]. I Kr is named as such because it is rapidly activating and the currents are characteristically inwardly rectifying due to its unique inactivation properties [62].…”