Effect Of Age-related Changes Of Gap Junction Protein On Ventricular Arrhythmia In Rats

Objective To investigate the age-related changes of gap junction protein-connexin43 (Cx43) in rats and their effect on the high incidence of ventricular arrhythmia in aged rats. Method 64 healthy male Fischer 344 (F344) rats were randomly picked from four groups(n=16 each), which are respectively 3-6(juvenile),9-12(young-adult), 18-21(middle-aged)and 24-26(aged) months old. The incidence rate of ventricular arrhythmia was recorded by monitoring their limb-lead ECG. Morphological changes of ventricular myocardium were observed under optical microscope after dyed with HE and Masson's stain. The distribution of Cx43 and nonphosphorylated connexin 43(NP-Cx43)was observed by confocal immunofluorescence microscopy; the amount of Cx43 and NP-Cx43 was assessed by Western-Blot. Result The incidence rate of ventricular arrhythmia in middle-aged (18-21 months) and aged rats (24-26 months) was 12.5%, 75% respectively, which were statistically significant differences(P<0.01).Besides, The incidence rate of ventricular arrhythmia of aged ones was much higher than the rest two relatively younger groups (P<0.01); and their ventricular muscle cells were hypertrophy and arrayed sparsely and disorderly with hyperplasia of connective tissues. The distribution of Cx43 changed from end-to-end to disorderly arrayed while the total amount of Cx43 (Total-Cx43) decreased as aging (F=21.43,P<0.01); the amount of each respectively was (0.29±0.08,0.19±0.06,0.15±0.05,0.12±0.05). The expression of NP-Cx43 was 0.53±0.18,0.44±0.12,0.34±0.10,0.43±0.07, respectively (F=6.65,P<0.01) and in middle-aged rats was amazingly decreased than juvenile and aged rats (P <0.05). Conclusion For aged person, the high incidence rate of ventricular arrhythmia may be associated with ventricular myocardium reconstruction, disarrangement of ventricular muscle cells and gap junction proteins, decreased expression amount of Cx43 and relatively increased of NP-Cx43.