POSTNATAL CHANGES IN T-TYPE CALCIUM CURRENT-DENSITY IN RAT ATRIAL MYOCYTES

被引:71
作者
XU, XP [1 ]
BEST, PM [1 ]
机构
[1] UNIV ILLINOIS,SCH MED,URBANA,IL 61801
来源
JOURNAL OF PHYSIOLOGY-LONDON | 1992年 / 454卷
关键词
D O I
10.1113/jphysiol.1992.sp019285
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1. Postnatal changes in Ca2+ current were studied in voltage clamped atrial myocytes isolated from Sprague-Dawley rats. T- and L-type Ca2+ currents were identified using standard electrophysiological and pharmacological techniques. Cells were studied from seven groups of male and six groups of female rats ranging in age from 3 to 14 weeks. 2. The density of atrial T-type Ca2+ current showed significant variation during postnatal development, with a maximum density reached at 4.5-5 weeks. At this age, T-current density was 1.44 +/- 0.11 pA/pF (n = 23) for cells isolated from male and 1.25 +/- 0.09 pA/pF (n = 25) for cells isolated from female animals in bathing solutions containing 2 mm-Ca2+. T-current density in atrial cells isolated from younger animals (3.5 weeks postnatal) averaged 1.22 +/- 0.06 (n = 18) and 1.00 +/- 0.05 pA/pF (n = 22) or 85 and 80 % of the maximum seen at 4.5-5 weeks for male and female rats, respectively. For rats older than 13 weeks, the average T-current density in atrial cells was 0.50 +/- 0-03 (n = 18) and 0.51 +/- 0-02 pA/pF (n = 35) or 35 and 41 % of the maximum seen at 4.5-5 weeks for male and female rats, respectively. 3. In contrast to the T-type current, the density of atrial L-type Ca2+ current remained unchanged in rats from 3 to 14 weeks old. L-type current averaged 8.2 +/- 0-2 (n = 134) in male and 7.9 +/- 0.2 pA/pF (n = 102) in female rats. 4. Fluctuation analysis was used to estimate single T-channel current levels in 4.5- and 7.5-week-old male rats. While the T-current density differed by 70 % at these two postnatal ages, no significant difference (P > 0.2) in single channel current was found. Single channel current was 0.12 +/- 0.01 pA (n = 9) for cells from 4.5-week-old and 0.13 +/- 0.01 pA (n = 7) for cells from 7.5-week-old rats. Currents were stimulated by test pulses from - 80 to - 30 mV at 5 mm-Ca2+. 5. No postnatal changes were seen in either the kinetics of activation or inactivation of macroscopic T-current. The time to peak current was 9.2 +/- 0.4 (n = 9) and 9.2 +/- 0.5 ms (n = 7) for cells isolated from 4-5- and 7.5-week-old rats, respectively. The time constant of inactivation of current was 21.6 +/- 1.1 (n = 9) and 22-5 +/- 1.6 ms (n = 7). 6. The finding that neither macroscopic current kinetics nor single channel current amplitude varied between cells suggests that the differences in T-current density seen at different postnatal ages are attributable to a change in channel density rather than a change in single channel conductance or gating. 7. T-current density is closely correlated with heart growth rate. For both male and female rats. T-current density is highest during the peak in growth rate that occurs at about postnatal week 5 and lowest when the growth rate approaches zero at adulthood. The maximum T-current density was 15 % higher for cells isolated from male rats (1.44 pA/pF) than those isolated from females (1.25 pA/pF). The maximum growth rate was 34 % higher in the male animals (9.8 g/day) as compared to that for the females (7.3 g/day). 8. These results demonstrate that T- and L-type Ca2+ current densities are differentially regulated in atrial myocytes during postnatal growth. Constant L-current density may be important for maintaining action potential shape and/or contractile activation as myocyte size increases. The significance of the positive correlation between atrial T-type Ca2+ current density and heart growth rate is unknown. However, our results are consistent with the notion that T-type Ca2+ current density is either regulated by. or itself regulates, a process associated with postnatal growth.
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页码:657 / 672
页数:16
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