Figure 3.

Intracellular calcium rise induced by calcium stressors. A, Simplified diagram showing how each treatment raises intracellular calcium ([Ca]_i), following the method of Akerman and Nicholls (1981). Left, Veratridine/ouabain/[Ca]_ex (voca) is a mixture of 1 μm veratridine, 100 μm ouabain, and 10 mm CaCl₂. Veratridine is a use-dependent Na⁺ channel opener. Na⁺ influx depolarizes the plasma membrane activating voltage-activated Ca²⁺ channels. Further Ca²⁺ entry occurs via reversal of the plasma membrane Ca²⁺/Na⁺ exchanger. The high cytosolic Na⁺ activates the mitochondrial Ca²⁺/Na⁺ exchanger, enhancing dissipative mitochondrial Ca²⁺ cycling (Nicholls and Scott, 1980). Right, [K]_ex/[Ca]_ex (kca) is a mixture of 30 mm KCl and 10 mm CaCl₂. High external K⁺ depolarizes the plasma membrane activating voltage-activated Ca²⁺ channels. Note that Na⁺ channels immediately inactivate. The plasma membrane Na⁺/Ca²⁺ exchanger reverses due to the high external Ca²⁺ and the collapse of the plasma membrane potential. Cytosolic Na⁺ remains low, limiting mitochondrial Ca²⁺ cycling but resulting in extensive matrix Ca²⁺ loading (Akerman and Nicholls, 1981). B, The treatment-induced synaptosomal free [Ca]_i increase was monitored for 25 min using fura 4F-AM as calcium indicator. White diamonds, Cortical synaptosomes from WT mice; black diamonds, cortical synaptosomes from J20 mice; white circles, hippocampal synaptosomes from WT mice; black circles, hippocampal synaptosomes from J20 mice. Data are means ± SE (n = 5 biological replicates each the average of 3 technical replicates).