Role of large-conductance calcium-activated potassium channels of coronary arteries in heart preservation.

Abstract

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.

• Authors: Jian-Guo Han, Qin Yang, Xiao-Qiang Yao, Yiu-Wa Kwan, Bing Shen, Guo-Wei He
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 28 Issue 10 Pg. 1094-101 (Oct 2009) ISSN: 1557-3117 [Electronic] United States
• PMID: 19782293 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Large-Conductance Calcium-Activated Potassium Channels
• Organ Preservation Solutions
• Peptides
• iberiotoxin

Topics

• Animals
• Cells, Cultured
• Coronary Vessels (physiology)
• Female
• Heart (physiology)
• Hyperkalemia (physiopathology)
• Large-Conductance Calcium-Activated Potassium Channels (antagonists & inhibitors, drug effects, physiology)
• Male
• Models, Animal
• Muscle, Smooth, Vascular (physiology)
• Myocardial Reperfusion Injury (physiopathology)
• Organ Preservation Solutions
• Patch-Clamp Techniques
• Peptides (pharmacology)
• Swine
• Vasodilation (drug effects, physiology)