Fig. 1.

Nuclear and cytosolic pathways controlling nuclear Ca²⁺ homeostasis in cardiomyocytes. Different pathways can lead to nuclear Ca²⁺ signals. Pathway 1: InsP₃ is generated by PLC either in the plasma membrane or in peri/intra-nuclear compartments. Pathway 2: InsP₃ can diffuse in and out of the nucleus. Pathway 3: InsP₃ from cytosolic or nuclear origin triggers Ca²⁺ release inside and/or outside the nucleus. Pathway 4: Ca²⁺ triggers Ca²⁺ release from RyRs in the cytoplasm or in the nucleus of cardiomyocytes (nuclear RyR is present only in neonatal cardiac myocytes). Pathway 5: Ca²⁺ diffusion from the cytosol can also generate nuclear Ca²⁺ transients and vice versa.