Figure 6.

BayK-induced Fos expression in WT and Ca_v1.2DHP–/– mice. Mice were injected with vehicle or BayK solution (WT, 2 mg/kg; mutants, 4 mg/kg) and Fos expression was quantified by immunohistochemistry as described in Methods. (A) DS, dorsal striatum; Ci, cingulate cortex; LV, lateral ventricle. Magnification, ∞40. Inset shows higher magnification of boxed areas. (B) Fos expression after BayK (right) or vehicle (left) application in the nucleus accumbens. aca, anterior commissure, anterior. Magnification, ∞100. Inset magnification, ∞800. (C) Fos expression after BayK (right) or vehicle (left) application in the BNST. Magnification, ∞100. Inset magnification, ∞800 (boxed area in the lateral division). acp, anterior commissure, posterior. (D) Stimulation of I_Ba through Ca_v1.2 (Ca_v1.2_WT), mutant Ca_v1.2 (Ca_v1.2_MUT), and Ca_v1.3 by BayK after heterologous expression under identical conditions in tsA-201 cells as described (15). Based on DHP pharmacokinetic data in mice (53), we calculated BayK concentration in brain to reach concentrations between ∼7 ∝M (peak concentration) and ∼1 ∝M (after three elimination half-lives). All data were significantly different from 1 (control before drug application) (P < 0.05; one-sample Student's t test) except Ca_v1.2_MUT, 1 ∝M and 5 ∝M BayK).