Role of large-conductance calcium-activated potassium channels of coronary arteries in heart preservation.
BACKGROUND
Large-conductance calcium-activated potassium channels (BK(Ca)) of vascular smooth muscle cells (VSMCs) play an important role in the regulation of vascular tone. We tested the hypotheses that the alteration of arterial relaxation after exposure to ischemia or hyperkalemia is attributable to the alteration in the activities of BK(Ca) by using the patch-clamp technique and force measurement.


METHODS
VSMCs were enzymatically isolated from porcine coronary arteries, with the primary cultures used for patch-clamp study. BK(Ca) currents were recorded in a whole-cell configuration (n = 5 in each group). The BK(Ca) activator NS1619 (-7 to -4.5 logM)-induced relaxation was studied myographically in small porcine coronary arteries (n = 6 per group). The effects of global ischemia for 1 hour and hyperkalemia (20 to 120 mmol/liter) were tested.


RESULTS
Ischemia for 1 hour markedly reduced the BK(Ca) current from 119.8 +/- 11.4 pA/pF to 86.0 +/- 3.7 pA/pF (p < 0.05). The rise of extracellular K(+) resulted in increased BK(Ca) currents in a concentration-dependent manner (5.4 mmol/liter: 31.6 +/- 3.4 pA/pF; 20 mmol/liter: 73.6 +/- 11.4 pA/pF; 60 mmol/liter: 108.6 +/- 20.6 pA/pF; 120 mmol/liter: 135.2 +/- 20.5 pA/pF; p < 0.05). NS1619-induced relaxation was suppressed by ischemia (71.4 +/- 2.2% vs 95.3 +/- 1.6%; p < 0.01) and was inferior in K(+) pre-contraction, as compared with U(46619) (a thromboxane A(2) mimetic) pre-contraction (p < 0.05).


CONCLUSIONS
In coronary circulation: (1) the BK(Ca) current density and related vasorelaxation are reduced after ischemia; and (2) hyperkalemia induces dual effects; the depolarization obscures the compensatory increase of the BK(Ca) activity. These findings imply that BK(Ca) activators may be used in cardioplegia or heart preservation solutions to protect the function of this ion channel.
Department of Surgery, Chinese University of Hong Kong, Hong Kong SAR, China.
Jian-Guo
JG
Han
Qin
Q
Yang
Xiao-Qiang
XQ
Yao
Yiu-Wa
YW
Kwan
Bing
B
Shen
Guo-Wei
GW
He
D000818:Animals; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000502:physiology*; D005260:Female; D006321:Heart / Q000502:physiology*; D006947:Hyperkalemia / Q000503:physiopathology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D019188:Organ Preservation Solutions; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D051036:Large-Conductance Calcium-Activated Potassium Channels; D019188:Organ Preservation Solutions; D010455:Peptides; C064719:iberiotoxin