Ryanodine Receptor Channelopathies: The New Kid in the Arrhythmia Neighborhood

Some of these cardiac diseases are acquired as cardiac hypertrophy, which develops as an adaptation of the heart to diseases that challenge the heart work chronically. Cardiac hypertrophy often degenerates in heart failure (HF), the final outcome of most cardiovascular diseases. Chronic HF prevalence is increasing in western countries, with only 25% of men and 38% of women surviving 5 years after the onset of clinical signs. Quality of life is hampered by the reduced pump function, which can also lead to death. However, half of deceases in HF patients are sudden due to cardiac arrhythmia. During cardiac pathology, altered activity of the cardiac, type 2, ryanodine receptor (RyR2) may generate arrhythmia and sudden death. This risk is high in HF where there is a profound remodeling of Ca2+ cycling, and alterations in transmembrane Ca2+ influx, Ca2+ release or/and sarcoplasmic reticulum (SR) Ca2+-load underlie systolic dysfunction (Gomez et al., 1997; Benitah JP, 2002). Thus, when dealing with HF and poor cardiac outcomes, it is a need to better understand the mechanisms of cardiac arrhythmia in order to efficiently treat these patients. However, a large number of inherited arrhythmogenic syndromes that cause sudden death have been characterised. Some are associated with structural heart disease, such as familial hypertrophic cardiomyopathy and arrythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Others do not produce structural heart disease and so are difficult to detect. Most of these cardiomyopathies are due to mutations in plasmalemmal cardiac ion channels, mainly the Na+ channel and several K+ channels (Lehnart et al., 2007). These mutations promote arrhythmogenesis by altering the action potential (AP) duration, which therefore may enhance the propensity of arrhythmic activity via the development of early after depolarizations (EADs). However, the recent finding of mutations in the Ca2+ release channel (RyR2) associated with catecholaminergic polymorphic ventricular tachycardia