RYR2 and atrial fibrillation: Although in atrial myocytes, L-type Ca2+ channels (LTCC) are equally distributed in and out of the tubular system [66], AF-associated cell hypertrophy and structural changes in the sarcolemma and RyR2 microdomains [67,68] may affect LTCC function, Ca2+-induced Ca2+-release events, RyR2 coupling to LTCC, PDE microdomains, RyR2 Ca2+ sensitivity and CaMKII activity.