{'fraction_non_alphanumeric': 0.016874541452677916, 'fraction_numerical': 0.003668378576669112, 'mean_word_length': 5.786069651741293, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Ryanodine receptors as pharmacological targets for heart disease

AbstractCalcium release from intracellular stores plays an important role in the regulation of muscle contraction and electrical signals that determine the heart rhythm. The ryanodine receptor (RyR) is the major calcium (Ca2+) release channel required for excitation-contraction coupling in the heart. Recent studies have demonstrated that RyR are macromolecular complexes comprising of 4 pore-forming channel subunits, each of which is associated with regulatory subunits. Clinical and experimental studies over the past 5 years have provided compelling evidence that intracellular Ca2+ release channels play a pivotal role in the development of cardiac arrhythmias and heart failure. Changes in the channel regulation and subunit composition are believed to cause diastolic calcium leakage from the sarcoplasmic reticulum, which could trigger arrhythmias and weaken cardiac contractility. Therefore, cardiac RyR have emerged as potential therapeutic targets for the treatment of heart disease. Consequently, there is a strong desire to identify and/or develop novel pharmacological agents that may target these Ca2+ signaling pathways. Pharmacological agents known to modulate RyR in the heart, and their potential application towards the treatment of heart disease are discussed in this review.