Figure 2.

Nonlinear baseline Ca²⁺-dependent response to AngII stimulus, in which low cytosolic Ca²⁺ baseline levels resulted in an increase in cytosolic Ca²⁺ and high cytosolic Ca²⁺ levels resulted in a decrease in cytosolic Ca²⁺ levels. (A) Schematic of Ca²⁺ regulatory dynamics. (B) Dynamic traces of cytosolic Ca²⁺ as a function of change in the rate constant of a Ca²⁺ transport into the ER $\left(k_{\text{ER}}^{{\text{Ca}}^{2+}}\right)$. (Solid lines) Time period where 100 nM AngII was applied; (shaded lines) steady-state levels preceding AngII application. Decreasing the $k_{\text{ER}}^{{\text{Ca}}^{2+}}$ from 3600 to 36 μm⁻² s⁻¹ increases the Ca²⁺ baseline levels from ∼72 to 136 nM (dotted line). (C) Dynamic traces of unbound calcium buffer levels as a function of change in $k_{\text{ER}}^{{\text{Ca}}^{2+}}$. For plot details, see (B). Decrease in $k_{\text{ER}}^{{\text{Ca}}^{2+}}$ drains out all stored Ca²⁺ in the buffer before AngII application (total capacity of the saturated buffer = 9091 nM). (D) AngII dose-dependence of cytosolic Ca²⁺ response for low cytosolic Ca²⁺ baseline condition. (Inset, top right) Intracellular calcium tracing from primary cultures of neonatal rat sympathetic neurons when exposed to 3 min AngII pulses (10 pM) for low baseline condition (27). (E) Upstream responses of PLCβ and IP₃, and downstream kinase responses of PKC and CaMKII for the low Ca²⁺ baseline condition. (F) AngII dose-dependence of cytosolic Ca²⁺ response for high cytosolic Ca²⁺ baseline condition. (Inset, bottom-right panel) Intracellular calcium tracings taken from cells (see D for details) with a higher baseline (>200 nM). (G) High Ca²⁺ baseline condition upstream responses of PLCβ and IP₃, and downstream kinase responses of PKC and CaMKII.