Postnatal changes in T‐type calcium current density in rat atrial myocytes.

Abstract

SUMMARY1. 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±+003 (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+±02 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 + 001 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 + 05 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 MS 9754 X. XU AND P. M. BEST 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 d...

Ca2+ currents in cardiac myocytes: Old story, new insights

“…frog, calf, cat, rabbit, ferret, mouse, rat, human (Argibay et al, 1988;Bean, 1989;Nuss and Houser, 1993;Yuan and Bers, 1994;Yuan et al, 1996;Nascimento, 1996;Li et al, 1999;Chen et al, 2002) but has been described in modest amounts in guineapig (Mitra and Morad, 1986;Sipido et al, 1998a). I CaT is present in atrial myocytes from frog, dog, cat, rat and guinea pig (Wu and Lipsius, 1990;Romanin et al, 1992;Xu and Best, 1992;Alvarez et al, 1996;Yue et al, 1999), but not human (Ouadid et al, 1991), heart.…”

Development of Excitation-Contraction Coupling in Cardiomyocytes

“…In immature or developing cardiomyocytes, the appearance of T-type Ca 2ϩ current is relatively high. For example, during the postnatal development of rat atrial myocytes, the density of T-type Ca 2ϩ current is well correlated with growth rate [12]. It appears that an increased expression of Ttype current is closely related to cellular growth and/or hypertrophy.…”

Immunodetection of α1E Voltage-gated Ca2+ Channel in Chromogranin-positive Muscle Cells of Rat Heart, and in Distal Tubules of Human Kidney

“…Recent reports have shown that T-type Ca 2ϩ currents not only contribute to pacemaking (Irisawa et al 1993) but also might be able to more directly trigger Ca 2ϩ release from sarcoplasmic reticulum in guinea pig (Sipido et al 1998) and canine Purkinje myocytes (Zhou and January 1998). In this regard, it might be interesting to investigate the IGF-induced T-type currents (Piedras-Rentería et al 1997), which perhaps are involved in peptide hormone secretion during differentiation of the atrial myocytes in culture (Xu and Best 1992). Future experiments might elucidate such a function using ␣1E-specific peptide toxins (Newcomb et al 1998).…”

“…Originally, the IGF-induced T-type Ca 2 ϩ current in heart has been related to ␣ 1E-induced Ca 2 ϩ inward currents, because antisense oligonucleotides against ␣ 1E mRNA inhibited the IGF-induced T-type current (Piedras-Rentería et al 1997). This T-type current is believed to be important mainly during development (Kawano and DeHaan 1991;Xu and Best 1992). Because recombinant ␣ 1E is not considered a typical T-type current (Randall and Tsien 1997;Nakashima et al 1998), the immunodetection of ␣ 1E as a method independent of RT-PCR amplification (Piedras-Rentería et al 1997;Mitchell et al 1999) should give additional insight into a possible physiological role for ␣ 1E in heart.…”