Objective: To investigate the roles and mechanisms of AKAP150/protein kinase Cα ( PKCα) signaling pathway in aerobic exercise-mediated regulation of L-type Cav1.2 channel (Cav1.2) function in cerebral arteries during hypertension. Methods; 12-week-old male spontaneously hypertensive rats ( SHR) and Wistar-Kyoto (WKY) rats were randomly assigned to sedentary (WKY-SED, SHR-SED) and exercise training (WKY-EX, SHR-EX) groups, respectively. Exercise groups were performed a moderate-intensity treadmill running. After 12 weeks, Western blot, immunofluorescence, patch-clamp whole-cell and single channel recording, qPCR were used to detect AKAP150/PKCα signaling pathway, Cav1.2 whole-cell and single channel currents, mRNA and protein expression of α1c subunits. AKAP150 smooth muscle-specific knockin mice (AKAP150 smKI) were constructed. The blood pressure was monitored in conscious WT and AKAP150 smKI mice using an implantable mouse telemetry system. Results; 1) Aerobic exercise significantly reduced body weight and blood pressure in SHR-EX. 2) The protein expression of AKAP150 in cerebral arterial smooth muscle was significantly up-regulated in SHR-SED, while down-regulated in SHR-EX. The protein expression of PKCα did not change in four groups, however, sarcolemmal PKCα translocation was significantly reduced in SHR-EX as compared with SHR-SED myocytes. 3 ) Aerobic exercise significantly decreased the colocalization rate of AKAP150 and PKCα in cerebral arterial myocytes from SHR-EX. 4) Aerobic exercise significantly inhibited SHR-induced increases in Cav1.2 currents in cerebral arterial myocytes, whereas the mRNA and protein expression of α1c subunits were unchanged. 5) Aerobic exercise significantly attenuated the Cav 1.2 channel nPo of SHR-EX cerebral arterial myocytes. 6) Inhibition of PKCα with Gö6976 decreased the Cav1.2 currents nearly 31%, 35%, 48% and 38% in WKY-SED, WKY-EX, SHR-SED and SHR-EX myocytes. 7) Application of the PKC activator PDBu increased a - 1.5-fold and 3.8 fold in the Cav1.2 channel nPo of WKY-SED and SHR-SED, respectively. Aerobic exercise significantly suppressed PDBu-evoked Cav 1.2 channel nPo in SHR-EX. 8) The systolic blood pressure, diastolic blood pressure and mean arterial pressure were significantly higher in AKAP150 smKI than in WT mice. Conclusions; Aerobic exercise effectively reduces blood pressure of SHR, inhibits sarcolemmal PKCα translocation, LTCC channel activity via suppression of AKAP150 protein expression, and ameliorates cerebral arterial function during hypertension. [ABSTRACT FROM AUTHOR]