Figure 8. Schematic depiction of the hypothesized relationship between cell membrane potential, L-type Ca²⁺ channel C terminus motion and ${\text{Ca}}_{\mathrm{i}}^{2+}$‘sensing’ by CaM and CaMK.

The L-type Ca²⁺ channel pore forming subunit (α_1C) is shown as a pair of open rectangles with a central pore. The C terminus protrudes into the cytoplasmic space from the right rectangle and the pore region and SR Ca²⁺ release channel (ryanodine receptor, dark trapezoid) are en face. Ca²⁺–CaM is depicted as a pair of stippled circles linked by a curved segment and activated CaMK is shown as a thick bar with curved ends bound to Ca²⁺–CaM. According to the hypothesized model, strong depolarizations motivate the C terminus to move away from the α_1C pore so that ${\text{Ca}}_{\mathrm{i}}^{2+}$ sensing is primarily from the SR. Weak depolarizations leave the C terminus in the vicinity of the pore where sensed ${\text{Ca}}_{\mathrm{i}}^{2+}$ is directly from I_Ca−L. Inactivation of SR Ca²⁺ release (by thapsigargin) results in significant impairment of ${\text{Ca}}_{\mathrm{i}}^{2+}$ sensing through CaM and CaMK during strong depolarizations, while ${\text{Ca}}_{\mathrm{i}}^{2+}$ from I_Ca−L is sufficient for Ca²⁺–CaM at weak depolarizations in the absence of SR Ca²⁺ release.