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Changes in I K, ACh single-channel activity with atrial tachycardia remodelling in canine atrial cardiomyocytes.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Voigt, Niels Maguy, Ange Yeh, Yung-Hsin Qi, Xiaoyan Ravens, Ursula Dobrev, Dobromir Nattel, Stanley |
| Copyright Year | 2008 |
| Abstract | AIMS Although atrial tachycardia (AT) remodelling promotes agonist-independent, constitutively active, acetylcholine-regulated K+-current (I K,ACh) that increases susceptibility to atrial fibrillation (AF), the underlying changes in I K,Ach channel function are unknown. This study aimed to establish how AT remodelling affects I K,ACh single-channel function. METHODS AND RESULTS I K,ACh single-channel activity was studied via cell-attached patch-clamp in isolated left atrial cardiomyocytes of control and AT (7 days, 400 min(-1)) dogs. Atrial tachycardia prolonged the mean duration of induced AF from 44 +/- 22 to 413 +/- 167 s, and reduced atrial effective refractory period at a 360 ms cycle length from 126 +/- 3 to 74 +/- 5 ms (n = 9/group, P < 0.001). In the absence of cholinergic stimulation, single-channel openings with typical I K,ACh conductance and rectification properties were sparse under control conditions. Atrial tachycardia induced prominent agonist-independent I K,ACh activity because of increased opening frequency (fo) and open probability (Po: approximately seven- and 10-fold, respectively, vs. control), but did not alter open time-constant, single-channel conductance, and membrane density. With maximum I K,ACh activation (10 micromol/L carbachol), channel Po was enhanced much more in control cells ( approximately 42-fold) than in AT-remodelled myocytes (approximately five-fold). The selective Kir3 current blocker tertiapin-Q (100 nmol/L) reduced fo and Po at -100 mV by 48 and 51%, respectively (P < 0.05 for each), without altering other channel properties, confirming the identity of I K,ACh. Atrial tachycardia had no significant effect on mRNA or protein expression of either of the subunits (Kir3.1, Kir3.4) underlying I K,ACh. CONCLUSION Atrial tachycardia increases agonist-independent constitutive I K,ACh single-channel activity by enhancing spontaneous channel opening, providing a molecular basis for AT effects on macroscopic I K,ACh observed in previous studies, as well as associated refractoriness abbreviation and tertiapin-suppressible AF promotion. These results suggest an important role for constitutive I K,Ach channel opening in AT remodelling and support its interest as a potential target for AF therapy. |
| Starting Page | 35 |
| Ending Page | 43 |
| Page Count | 9 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://watermark.silverchair.com/cvm051.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAa8wggGrBgkqhkiG9w0BBwagggGcMIIBmAIBADCCAZEGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM0E1w1sv7MFAlolqMAgEQgIIBYqxBz8nnTY_03c8vxj0cT7jlRZjbIMOXtWeHhMD7OlilGu1hnUgljMeeJ5QAb5Cjk2W8BjyiBkmILrTvyfbcxBp36SBbrP5-ZbDmp5XVmqJ_wOWz-NkL7XlW5CUBSMHL5RcP9fR-uiDIol5cKcGy4pxBuKkP_e2HqGJWKvyEhBF0J8c34avm73BaAd7iHHBdtjauQFEwKjVBmcSP1mGDVf923YAMMIcDaB7DratT3mwREkGlzVPlTJfMBjSgpsx_ItvhGbJXxKvSUIMZxUgmrbvDtll7Ar9l4pj6pKee79S24NBE3iBg4SUeW2TA11yS9ylj-iiUtS3Ln6AclGlRnE-SBsbOjB6dMr9A7oXqp6pKmjsHkxw--8cvgPSPF0hBW-WEhV8tb6x_RYEdyNSEo029V6-PXSnOqPcujo3A2VAUj01J7dW9t-w9JjIMgUt89KvqHR79zFbbjpInUXUSDd5P4A |
| PubMed reference number | 18006448v1 |
| Volume Number | 77 |
| Issue Number | 1 |
| Journal | Cardiovascular research |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Abbreviations Acetylcholine Atrial Fibrillation Atrial tachycardia Canis familiaris Carbachol Cerebrovascular accident Glucocorticoid-remediable aldosteronism Heart Atrium IK gene KCNJ5 gene Manuscripts Micromole Muscle Cells Myocytes, Cardiac Potassium Tachycardia, Ventricular Tissue membrane Ventricular Fibrillation channel activity protein expression tertiapin |
| Content Type | Text |
| Resource Type | Article |
