Acta Pharmacologica Sinica (2009) 30: 314-320; doi: 10.1038/aps.2009.7

Aim: To investigate the effects of docosahexaenoic acid (DHA) on large-conductance Ca²⁺-activated K⁺ (BK_Ca) channels and voltage-dependent K⁺ (K_V) channels in rat coronary artery smooth muscle cells (CASMCs).

Methods: Rat CASMCs were isolated by an enzyme digestion method. BK_Ca and K_V currents in individual CASMCs were recorded by the patch-clamp technique in a whole-cell configuration at room temperature. Effects of DHA on BK_Ca and K_V channels were observed when it was applied at 10, 20, 30, 40, 50, 60, 70, and 80 µmol/L. 

Results: When DHA concentrations were greater than 10 µmol/L, BK_Ca currents increased in a dose-dependent manner.  At a testing potential of +80 mV, 6.1%±0.3%, 76.5%±3.8%, 120.6%±5.5%, 248.0%±12.3%, 348.7%±17.3%, 374.2%±18.7%, 432.2%±21.6%, and 443.1%±22.1% of BK_Ca currents were increased at the above concentrations, respectively.  The half-effective concentration (EC₅₀) of DHA on BK_Ca currents was 37.53±1.65 µmol/L.  When DHA concentrations were greater than 20 µmol/L, K_V currents were gradually blocked by increasing concentrations of DHA.  At a testing potential of +50 mV, 0.40%±0.02%, 1.37%±0.06%, 11.80%±0.59%, 26.50%±1.75%, 56.50%±2.89%, 73.30%±3.66%, 79.70%±3.94%, and 78.1%±3.91% of K_V currents were blocked at the different concentrations listed above, respectively.  The EC₅₀ of DHA on K_V currents was 44.20±0.63 µmol/L.  

Conclusion: Allisartan is highly effective for BP reduction and organ protection with low toxicity.

Keywords: smooth muscle cell; large conductance Ca²⁺-activated K⁺ channel; voltage-gated K⁺ channel; docosahexaenoic acid; patch-clamp techniques