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Calcium-activated potassium channel family in coronary artery bypass grafts
Wen-Tao Sun1, Hai-Tao Hou1, Huan-Xin Chen1
1Center for Basic Medical Research & Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Insights
Calcium-activated potassium (KCa) channels are key in blood vessel dilation. This study found differences in KCa subtype distribution between internal thoracic artery and saphenous vein grafts, highlighting BKCa
Area of Science:
- Cardiovascular Physiology
- Molecular Biology
- Vascular Biology
Background:
- Coronary artery bypass graft (CABG) surgery relies on graft patency, influenced by vasodilatation.
- Calcium-activated potassium (KCa) channels regulate vascular tone, but their role in different graft types is not fully understood.
- Internal thoracic artery (ITA) and saphenous vein (SV) are common CABG conduits with distinct properties.
Purpose of the Study:
- To investigate the expression, distribution, and functional contribution of KCa channel subtypes (BKCa, IKCa, SKCa) in ITA and SV.
- To elucidate the role of these KCa channels in endothelium-smooth muscle interactions governing graft vasodilatation.
- To understand how KCa channel characteristics impact the postoperative performance of CABG grafts.
Main Methods:
- Real-time polymerase chain reaction and Western blot for KCa channel mRNA and protein.
- Immunohistochemistry to determine the tissue distribution of KCa channel subtypes.
- Wire myography to assess KCa subtype-mediated vasorelaxation.
Main Results:
- All KCa channel subtypes (BKCa, IKCa, SKCa) are expressed in both ITA and SV endothelium and smooth muscle.
- ITA shows greater smooth muscle abundance of BKCa and greater endothelial abundance of SKCa, unlike the even distribution in SV.
- BKCa significantly contributes to ITA vasodilatation, with a limited role in SV.
Conclusions:
- KCa channels are abundant in both ITA and SV, with distinct subtype distributions in vascular layers.
- The significant role of BKCa in ITA vasodilatation suggests its therapeutic potential for preventing ITA spasm post-CABG.
- Understanding these KCa channel differences can inform strategies to improve graft function and patient outcomes.
Objectives:
We examined the expression, distribution, and contribution to vasodilatation of the calcium-activated potassium (KCa) channel family in the commonly used coronary artery bypass graft internal thoracic artery (ITA) and saphenous vein (SV) to understand the role of large conductance KCa (BKCa), intermediate-conductance KCa (IKCa), and small-conductance KCa (SKCa) channel subtypes in graft dilating properties determined by endothelium-smooth muscle interaction that is essential to the postoperative performance of the graft.
Methods:
Real-time polymerase chain reaction and western blot were employed to detect the messenger RNA and protein level of KCa channel subtypes. Distribution of KCa channel subtypes was examined by immunohistochemistry. KCa subtype-mediated vasorelaxation was studied using wire myography.
Results:
Both ITA and SV express all KCa channel subtypes with each subtype distributed in both endothelium and smooth muscle. ITA and SV do not differ in the overall expression level of each KCa channel subtype, corresponding to comparable relaxant responses to respective subtype activators. In ITA, BKCa is more abundantly expressed in smooth muscle than in endothelium, whereas SKCa exhibits more abundance in the endothelium. In comparison, SV shows even distribution of KCa channel subtypes in the 2 layers. The BKCa subtype in the KCa family plays a significant role in vasodilatation of ITA, whereas its contribution in SV is quite limited.
Conclusions:
KCa family is abundantly expressed in ITA and SV. There are differences between these 2 grafts in the abundance of KCa channel subtypes in the endothelium and the smooth muscle. The significance of the BKCa subtype in vasodilatation of ITA may suggest the potential of development of BKCa modulators for the prevention and treatment of ITA spasm during/after coronary artery bypass graft surgery.
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