Back
Acta Physiologica 2012; Volume 204, Supplement 689
91st Annual Meeting of The German Physiological Society
3/22/2012-3/25/2012
Dresden, Germany
NUCLEAR CALCIUM SIGNALLING DURING THE DEVELOPMENT OF HYPERTENSION-INDUCED HYPERTROPHY IN RAT VENTRICULAR MYOCYTES
Abstract number: P016
Plackic1 *J., Pluteanu1 F., Kockskamper1 J.
1Philipps-Universitt Marburg, Pharmakologie und Klinische Pharmazie, Marburg, Germany
Question:
Hypertension is a major risk factor for developing cardiac hypertrophy and heart failure. We hypothesize that maladaptive remodelling in cardiomyocyte structure and Ca signalling begins early in hypertension and contributes to the initiation and progression of hypertrophy. To test this hypothesis we characterized cytoplasmic and nucleoplasmic Ca transients (CaTs) of ventricular myocytes from 1214 weeks old spontaneously hypertensive rats (SHR), i.e. shortly after the development of hypertension. Age-matched normotensive Wistar-Kyoto rats (WKY) served as controls.
Methodology:
Isolated ventricular myocytes were loaded with 8mM Fluo-4-AM (30min) and electrically stimulated at 1Hz. Cyto- and nucleoplasmic CaTs were recorded using linescan confocal imaging. Nuclear Ca stores were imaged in myocytes loaded with the low affinity Ca dye Mag-Fluo-4-AM (12mM, 120min).
Results:
Cardiomyocyte and nuclear sizes were significantly increased in SHR vs WKY indicating early development of hypertrophy. The number of nuclear envelope invaginations was unchanged in SHR compared to WKY (~3 per nucleus). SHR myocytes (n=18) exhibited significantly higher cytoplasmic (dF/Frest: SHR: 9.73±0.67 vs WKY: 6.74±0.29; P<0.01) and nucleoplasmic (dF/Frest: SHR: 6.99±0.50 vs WKY: 3.68±0.29; P<0.01) CaTs than WKY myocytes (n=49). The nucleoplasmic-to-cytoplasmic CaT ratio was increased in SHR (SHR: 0.74±0.03 vs WKY: 0.54±0.02; P<0.01). Furthermore, CaT decay was significantly faster both in cytoplasm and nucleoplasm of SHR myocytes.
Conclusion:
Profound changes in cyto- and nucleoplasmic CaTs occur in SHR myocytes shortly after the onset of hypertension indicating early remodelling of subcellular Ca homeostasis. The increase in nucleoplasmic Ca may be involved in Ca-dependent regulation of transcription and progression of hypertrophy.
To cite this abstract, please use the following information:
Acta Physiologica 2012; Volume 204, Supplement 689 :P016