Objectives This study aimed at investigating the cellular mechanism of isoproterenol (ISO) on delayed afterdepolarizations (DADs) and triggered activity (TA) of the noninfarcted myocardium in the myocardial infarcted rabbit model.Methods Rabbits with the left anterior descending coronary artery occlusion were prepared and recovered for 8 wk (healed myocardial infarction, HMI). Myocytes were isolated from regions of the noninfarcted left ventricular free wall. ISO was added to cellular surface by perfusion way. Action potentials and ion currents were recorded with whole-cell patch clamp. Results The results showed that treatment with ISO induced more DADs and TA events in HMI myocytes. Iti and ICa-L of myocytes treated with ISO were increased significantly compared with HMI cells, which contributed to DADs-related triggered arrhythmia. Conclusions The results suggested that more arrhythmia events of DADs and TA developed in myocytes with ISO treatment. The underlying mechanism was associated with the augment of Iu and calcium influxing.

This article reports the investigation of the effect of carvedilol (Car) on T-type calcium current (I(Ca,T)) of noninfarcted ventricular myocytes in rabbit models of healed myocardial infarction (HMI). Rabbits with left anterior descending artery ligation were prepared and allowed to recover for 8 weeks, as HMI group. Animals undergoing an identical surgical procedure without coronary ligation were served as the sham-operated group (sham group). Whole cell voltage-clamp techniques were used to measure and compare currents in cells from the different groups. Noting that I(Ca,T) density in HMI cells increased markedly to -2.36 +/- 0.12 pA/pF (at -30 mV) compared with cells of sham, where little I(Ca,T) (-0.35 +/- 0.02 pA/pF) was observed. Meanwhile, further analysis revealed a significant hyperpolarizing shift of steady-state activation curve of I(Ca,T) in HMI cells, where the time constants of deactivation were prolonged and the time of recovery from inactivation was shortened. Finally, the amplitude of I(Ca,T) was increased. Carvedilol (1 micromol x L(-1)) was found to decrease the amplitude of I(Ca,T) to -1.38 +/- 0.07 pA/pF through inhibiting process of I(Ca,T) activation. Furthermore, carvedilol delayed recovery from inactivation of I(Ca,T) and shortened the time constants of deactivation in HMI cells. This study suggested that the application of carvedilol in HMI cells contributes to the dynamic changes in I(Ca,T) and may account for reduction of incidence of arrhythmia after myocardial infarction.

OBJECTIVETo study the relationship between mitochondrial DNA (mtDNA) mutations and hypertension.

METHODSClinical data of two pedigrees with maternally transmitted hypertension was collected. Whole mtDNA sequence was analyzed.

RESULTSThe family members on the maternal side presented with various levels of hypertension, with the onset age ranging from 44 to 55 years old. Analysis of the mtDNA sequence of the two families members showed all patients have carried a matrilineal 4329C> G mutation of the tRNA(Ile) and tRNA(Gln) genes. The same mutation was not found in 366 healthy controls. The 4329C site of mtDNA is highly conserved across species, and has been associated with the fidelity of amino acid accept arm of the tRNAs, as well as functionality and stability in the formation of tRNAs.

CONCLUSIONThe 4329C> G point mutation in tRNA(Ile) and tRNA(Gln) probably has contributed to the pathogenesis of hypertension, possibly in association with other modifying factors.

Adult ; Base Sequence ; DNA Mutational Analysis ; DNA, Mitochondrial ; chemistry ; genetics ; Family Health ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Hypertension ; genetics ; Male ; Middle Aged ; Molecular Sequence Data ; Pedigree ; Point Mutation ; RNA, Transfer, Gln ; genetics ; RNA, Transfer, Ile ; genetics ; Sequence Homology, Amino Acid