Ryanodine receptor type 2 (RYR2) (RYR2)

Ryanodine receptor type 2 (RYR2) is a massive homotetrameric calcium release channel situated on the sarcoplasmic reticulum of cardiac myocytes [1]. It is the essential mediator of calcium-induced calcium release (CICR), a process where a small trigger influx of calcium via L-type calcium channels causes a large-scale release of stored calcium into the cytoplasm to drive heart muscle contraction [2]. Dysfunction of RYR2, often characterized by a 'leaky' state during the resting phase (diastole), is a primary driver of life-threatening conditions such as catecholaminergic polymorphic ventricular tachycardia (CPVT) and heart failure [3][4]. Therapeutic intervention aims to stabilize the channel's gated mechanism to prevent these spontaneous calcium leaks without interfering with the necessary calcium release during the heartbeat [5]. Both clinically available drugs like flecainide and experimental stabilizers known as Rycals are used or being investigated to modulate RYR2 function in patients with inherited arrhythmias and chronic heart disease [6].

Other names

Ryanodine receptor 2Cardiac ryanodine receptorCardiac muscle ryanodine receptor-calcium release channelhRyR2Type 2 ryanodine receptor

Pharmacological agents target RYR2 primarily to stabilize the channel's closed state during diastole, thereby preventing pathological calcium leakage from the sarcoplasmic reticulum that leads to triggered arrhythmias and contractile dysfunction.