Ion channel function in disease.
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Animals↗
Biomedical subjects
C D Jeck
Publications and source records attributed to C D Jeck.
Decreased expression of calmodulin mRNA in human end-stage heart failure.
Calmodulin (CaM) is the primary Ca2+ regulatory protein in cardiac cells, thus alterations in calmodulin would greatly influence the contractile response and may play a role in the abnormal calcium handling observed in human heart failure. We used Northern blot analysis to determine changes in calmodulin mRNA expression in left ventricular tissues isolated from 20 failing and four control human hearts. Only hearts with failure due to idiopathic dilated cardiomyopathy (DCM) or ischaemic heart disease (IHD) were studied. A human calmodulin cDNA probe 95% homologous to Type 3 CaM was used, which hybridized to a single 2.3 kb mRNA. CaM mRNA levels were expressed as a function of total RNA, as determined by hybridization to an 18S cDNA probe, and as a function of myocyte specific mRNA, as determined by hybridization to a myosin heavy chain (MHC) cDNA probe. In both DCM and IHD, CaM mRNA expression relative to total RNA (CaM/18S), was significantly decreased (45% and 61%, respectively) compared to control hearts. CaM mRNA expression in DCM tissues was also significantly decreased (45%) relative to myocyte specific mRNA (CaM/MHC), when compared to control hearts. In IHD, CaM mRNA was not significantly decreased in relation to myocyte specific mRNA, which suggests a greater loss of myocytes or contractile proteins in IHD as compared with DCM. The decreased expressed of CaM mRNA observed in failing hearts could affect many Ca(2+)-dependent processes, and contribute to the inability of these hearts to handle Ca2+ in a viable manner.
Adult↗
Age-related appearance of outward currents may contribute to developmental differences in ventricular repolarization.
Ventricular repolarization significantly influences contractility, refractoriness, and ion channel state. Factors affecting repolarization will thus affect these secondary phenomena. To understand the influence of age on ventricular repolarization, we studied neonatal, young, and adult dogs using electrocardiogram, action potential, and whole-cell voltage-clamp recordings from single epicardial myocytes. Hearts of neonatal and 57-58-day-old dogs require a significantly longer time for repolarization than those of adult dogs, as determined by analysis of rate-corrected QT and JT (QT minus QRS) intervals. Epicardial action potentials of neonates are significantly longer than those of adults, as determined by measurements of duration at 50% and 90% repolarization. The adult action potential is characterized by a large phase 1 notch that is absent from neonatal recordings. This notch develops between 58 and 64 days of age, and by 64-68 days of age, it is equal to that in adults. In addition, action potentials recorded from adult and young epicardial muscle are more greatly affected by rapid pacing and superfusion of 2 mM 4-aminopyridine than are potentials recorded from neonatal tissue. Whole-cell voltage-clamp recordings reveal a 4-aminopyridine-sensitive transient outward current in adult myocytes that is absent from neonatal myocytes. The correlation between developmental changes in the 4-aminopyridine-sensitive current, the action potential, and the QT interval suggests that the transient outward current may be an important determinant in the relation between age and repolarization.
4-Aminopyridine↗
Use-dependent effects of lidocaine in neonatal and adult ventricular myocardium.
Tissues from different areas of the heart and from animals of different ages are not uniform in regard to their action potential characteristics. Thus, they would not be expected to respond homogeneously to pathological processes or cardioactive drugs. Our objectives were to determine the age-related changes in canine epicardial and guinea pig papillary muscle transmembrane potentials and to determine the age-related effects of lidocaine on these tissues. Standard microelectrode techniques were used. We found the neonatal canine epicardial action potential plateau to be more positive and rounded and the action potential duration to be longer than that of the adult epicardium. In contrast, guinea pig papillary muscles did not show any differences in neonatal and adult transmembrane potentials. Significant age-related differences in the use-dependent effects of lidocaine were found in the canine epicardial tissue. The neonatal epicardium reached a steady-state level of block more rapidly and recovered from this block more slowly when compared to the adult epicardium. The guinea pig papillary muscles showed no age-related differences in the kinetics of use-dependent lidocaine block. These data suggest that age-related differences in the voltage-time course of the action potential plateau and repolarization may be largely responsible for the age-related differences seen in lidocaine's effects on canine epicardium.
Action Potentials↗