| First Author | Mahida S | Year | 2014 |
| Journal | Cardiovasc Res | Volume | 101 |
| Issue | 2 | Pages | 326-34 |
| PubMed ID | 24296650 | Mgi Jnum | J:220058 |
| Mgi Id | MGI:5632077 | Doi | 10.1093/cvr/cvt269 |
| Citation | Mahida S, et al. (2014) Overexpression of KCNN3 results in sudden cardiac death. Cardiovasc Res 101(2):326-34 |
| abstractText | BACKGROUND: A recent genome-wide association study identified a susceptibility locus for atrial fibrillation at the KCNN3 gene. Since the KCNN3 gene encodes for a small conductance calcium-activated potassium channel, we hypothesized that overexpression of the SK3 channel increases susceptibility to cardiac arrhythmias. METHODS AND RESULTS: We characterized the cardiac electrophysiological phenotype of a mouse line with overexpression of the SK3 channel. We generated homozygote (SK3(T/T)) and heterozygote (SK3(+/T)) mice with overexpression of the channel and compared them with wild-type (WT) controls. We observed a high incidence of sudden death among SK3(T/T) mice (7 of 19 SK3(T/T) mice). Ambulatory monitoring demonstrated that sudden death was due to heart block and bradyarrhythmias. SK3(T/T) mice displayed normal body weight, temperature, and cardiac function on echocardiography; however, histological analysis demonstrated that these mice have abnormal atrioventricular node morphology. Optical mapping demonstrated that SK3(T/T) mice have slower ventricular conduction compared with WT controls (SK3(T/T) vs. WT; 0.45 +/- 0.04 vs. 0.60 +/- 0.09 mm/ms, P = 0.001). Programmed stimulation in 1-month-old SK3(T/T) mice demonstrated inducible atrial arrhythmias (50% of SK3(T/T) vs. 0% of WT mice) and also a shorter atrioventricular nodal refractory period (SK3(T/T) vs. WT; 43 +/- 6 vs. 52 +/- 9 ms, P = 0.02). Three-month-old SK3(T/T) mice on the other hand displayed a trend towards a more prolonged atrioventricular nodal refractory period (SK3(T/T) vs. WT; 61 +/- 1 vs. 52 +/- 6 ms, P = 0.06). CONCLUSION: Overexpression of the SK3 channel causes an increased risk of sudden death associated with bradyarrhythmias and heart block, possibly due to atrioventricular nodal dysfunction. |
