Effects of docosahexaenoic acid on large-conductance Ca2+-activated K+ channels and voltage-dependent K+ channels in rat coronary artery smooth muscle cells.
OBJECTIVE
To investigate the effects of docosahexaenoic acid (DHA) on large-conductance Ca(2+)-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 micromol/L.


RESULTS
When DHA concentrations were greater than 10 micromol/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 (EC(50)) of DHA on BK(Ca) currents was 37.53+/-1.65 micromol/L. When DHA concentrations were greater than 20 micromol/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 EC(50) of DHA on K(V) currents was 44.20+/-0.63 micromol/L.


CONCLUSIONS
DHA can activate BK(Ca) channels and block K(V) channels in rat CASMCs, and the EC(50) of DHA for BK(Ca) channels is lower than that for K(V) channels; these findings indicate that the vasorelaxation effects of DHA on vascular smooth muscle cells are mainly due to its activation of BK(Ca) channels.
Lai
Li-hong
LH
Department of Cardiology, First Affiliated Hospital of Soochow University, Suzhou, China.
Wang
Ru-xing
RX
Jiang
Wen-ping
WP
Yang
Xiang-jun
XJ
Song
Jian-ping
JP
Li
Xiao-rong
XR
Tao
Guo
G
D000818:Animals; D003331:Coronary Vessels / Q000033:anatomy & histology* / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D004281:Docosahexaenoic Acids