Exposure to microgravity leads to a sustained elevation in transmural pressure across cerebral vasculature due to removal of hydrostatic pressure gradients. We hypothesized that ion channel remodeling in cerebral vascular smooth muscle cells (VSMCs) similar to that associated with hypertension may occur and play a role in the upward autoregulation of cerebral vessels during microgravity. Sprague-Dawley rats were subjected to 4-wk tail-suspension (SUS) to simulate the cardiovascular effect of microgravity. Large-conductance Ca²⁺-activated K⁺ (BKCa), voltage-gated K⁺ (K_V), and L-type voltage-dependent Ca²⁺ (Ca_L) currents of cerebral VSMCs of SUS were investigated using whole-cell voltage-clamp technique and compared with control (CON) rats. Under the same experimental conditions, K_V, BK_Ca, and Ca_L currents of cerebral VSMCs from adult SHR and WKY were also investigated. In SUS rats, K_V current density decreased as compared with CON [1.07±0.14 (n=22) vs. 1.31 ± 0.28 (n=16) pA/pF at +20 mV, P<0.05], and BK_Ca, and Ca_L current densities increased [BK_Ca, 1.70 ± 0.37 (n=23) vs. 0.88 ± 0.22 (n=19) pA/pF at +20 mV, P<0.05; Ca_L, -2.17 ± 0.21 (n=35) vs. -1.31 ± 0.10 (n=26) pA/pF at +10 mV, P<0.05]. Similar changes were also observed in SHR cerebral VSMCs compared with WKY: K_V current density decreased [1.03 ± 0.33 (n=9) vs. 1.62 ± 0.64 (n=9) pA/pF at +20 mV, P<0.05]; and BK_Ca, and Ca_L current densities increased [BKCa, 2.54 ± 0.47 (n=11) vs. 1.12 ± 0.33 (n=12) pA/pF at +20 mV, P<0.05; Ca_L, -3.99 ± 0.53 (n=12) vs. -2.28 ± 0.20 (n=10) pA/pF at +20 mV, P<0.05]. These findings support our hypothesis and their impact on space cardiovascular research has been discussed.