Comparison of Ito in young and adult human atrial myocytes: evidence for developmental changes

Abstract

In an effort to understand the ionic basis for the developmental changes that have been reported to occur in the configuration of the human atrial action potential, we characterized the transient outward current (Ito) and the inward rectifier current in atrial myocytes isolated from 20 young (ages 1 day-2.5 yr) and 8 adult (11-68 yr) human hearts using the whole cell patch-clamp technique. We found evidence for statistically significant (P < 0.05) age-related changes in the Ito, including 1) the presence of an Ito in only 67% of the cells isolated from young hearts vs. 100% of the cells isolated from adult hearts, 2) an almost twofold increase in the current density of Ito in adult cells vs. young cells, and 3) recovery kinetics that are approximately twofold slower in young myocytes relative to adult myocytes. In contrast, there were no age-related changes found in the current density of the inward rectifier current or the sustained current measured after the decay of Ito. These results suggest important current-dependent changes that occur with age in human atria.

In Vitro Cardiovascular Effects of Dihydroartemisin-Piperaquine Combination Compared with Other Antimalarials

“…(i) Isolation of cardiac myocytes. Human myocytes were obtained from specimens of human right atrial appendage obtained during surgery from hearts of patients undergoing cardiopulmonary bypass (12). Samples were quickly immersed in a cardioplegic solution consisting of 50 mM KH 2 PO 4 , 8 mM MgSO 4 , 10 mM NaHCO 3 , 5 mM adenosine, 25 mM taurine, 140 mM glucose, and 100 mM mannitol, titrated to a pH of 7.4, and bubbled with 100% O 2 at 0 to 4°C.…”

Quinidine Interactions With Human Atrial Potassium Channels

“…19 Previous work by Wu et al 7 in rabbit myocytes has shown that age-related changes in the sensitivity of I K1 to quinidine may also occur. Although no developmental change in the characteristics of I K1 has been reported for human cardiac tissue, 12 it was difficult to rule out the possibility that postnatal changes in I K1 sensitivity to quinidine sensitivity may not also exist in human tissue. To define the effects of Comparison of the kinetics and voltage dependence of I to recovery from quinidine block in pediatric and adult myocytes.…”

“…Human atrial myocytes were isolated enzymatically from the obtained specimens. The isolation procedure was identical to that previously described by Crumb et al 12 and typically produced an initial yield of 40% to 60% rod-shaped, calcium-tolerant cells. Cells were used within 8 hours after isolation.…”

“…12 Because the time course over which I to undergoes its developmental change was not well defined, we compared values of I to amplitude obtained for 9 different age groups ranging in age between 0 to 1 month and 56 to 75 years. As demonstrated in Figure 1A, the amplitude of human atrial I to did not change significantly during the first 2 years of life, after which it doubled in amplitude between the ages of 2 and 11 years and then remained relatively constant until at least 75 years of age.…”

“…This supports the conclusion that quinidine's inhibitory effect on the total steady-state current ( Figure 3B) is exclusively due to quinidine-induced block of I Kur , whose density is known not to be age-independent. 12 Dose-response curves defining the inhibitory effect of quinidine on the total sustained outward current (I sus ϭI Kur ϩI ns ) in pediatric and adult myocytes also were defined from measurements of quinidine's effect on the sustained current at the end of an 800-ms pulse during a step to 60 mV. The IC 50 values obtained after fitting the data to the Hill equation were not significantly different between the 2 age groups (adult IC 50 ϭ6.6 mol/L; pediatric IC 50 ϭ5.1 mol/L; PϾ0.76).…”