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L6. The Sarcolemmal Adenosine Triphosphate-Sensitive Potassium Channel Underlies the Regulation of Hyperkalemic Cardioplegia-Induced Myocyte Swelling and Reduced Contractility
Sandip M Prasad, Gregory D. Byrd, Thomas P. Flagg, Jefferson Gomes, Ralph J. Damiano, Jr., Colin G. Nichols, Jennifer S. Lawton; St. Louis, MO
OBJECTIVES: Hyperkalemic cardioplegia has been shown to result in cardiomyocyte swelling and reduced cell contractility. These detrimental effects are eliminated by the addition of a non-specific adenosine triphosphate-sensitive K+ (KATP) channel opener. To identify whether the mitochondrial or sarcolemmal KATP channel is responsible, volume and contractility in isolated myocytes from wild-type and sarcolemmal KATP-deficient knockout mice were evaluated.
METHODS: Myocytes (n=40) were isolated from wild-type and knockout mice and were perfused for 20 minute periods with: (1) control 37°C Tyrode’s solution, (2) test solution, and (3) re-exposure to control solution. Test solutions were: (A) 9°C Plegisol and (B) 9°C Plegisol with 100 μmol/L of diazoxide, a mitochondrial-specific KATP channel opener. Cell volume and contractility were measured by digital video microscopy and edge-detection software at baseline and during the test solution and re-exposure periods.
RESULTS: Myocytes from wild-type mice, perfused with 9°C Plegisol, demonstrated significant cell swelling (11.2%, p<0.01) and diminished re-exposure contractility by all measures versus baseline. In this group, cell swelling and diminished contractility were significantly reduced by the addition of diazoxide. In knockout mice, Plegisol caused a reduced level of significant cell swelling (3.2%, p<0.01), and this was not ameliorated by diazoxide. Contractility was not affected in this group with the addition of either test solution.
CONCLUSIONS: The sarcolemmal channel is involved in the amelioration of cell swelling and reduced contractility following hyperkalemic cardioplegia. This channel likely maintains cellular volume homeostasis via potassium efflux from the cell, thereby preserving myocyte function. These findings cast doubt about the role of the mitochondrial KATP channel in myocyte homeostasis.
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WILD-TYPE |
Kir6.2 KNOCKOUT |
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9°C Plegisol |
9°C Plegisol + DZX |
9°C Plegisol |
9°C Plegisol + DZX |
| Contractility (20 min) |
|
|
|
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| % shortening |
- 34.8% ** |
5.6% |
6.0% |
10.2% |
| Velocity of shortening |
- 46.0% * |
- 9.4% |
- 3.7% |
-18.5% |
| Velocity of relengthening |
- 47.1% * |
- 10.6% |
7.7% |
-19.9% |
| Cell volume |
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|
|
|
| Test period |
11.6% * |
2.8% * |
3.2% * |
2.3% * |
| Reperfusion |
1.4% |
- 2.5% * |
-4.1% * |
- 4.4% * |
| All values are represented as a percentage difference from baseline. * p<0.01 vs. baseline, **p<0.05 vs. baseline |
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