Developmental changes in time course of recovery from inactivation in L-type calcium currents of rabbit ventricular myocytes

Abstract

Namiki T, Joyner RW, and Wagner MB. Developmental changes in time course of recovery from inactivation in L-type calcium currents of rabbit ventricular myocytes. Am J Physiol Heart Circ Physiol 292: H295-H303, 2007. First published August 25, 2006; doi:10.1152/ajpheart.00719.2006.-The mechanisms of recovery from inactivation of the L-type calcium current (ICa) are not well established, and recovery is affected by many experimental conditions. Little is known about developmental changes of recovery from inactivation of ICa. We studied developmental changes of recovery from inactivation in I Ca using isolated adult and newborn (1-4 days) rabbit ventricular myocytes. We used broken-patch and perforatedpatch techniques with physiological extracellular ionic concentrations of calcium and sodium and interpulse conditioning potentials of Ϫ80 or Ϫ50 mV. We also maximized ICa with forskolin. We found that recovery from inactivation did not differ between adult and newborn cells when either EGTA or BAPTA was used to buffer intracellular calcium. Maximizing ICa with forskolin slowed recovery from inactivation in newborn but not in adult cells. In contrast, when the intracellular buffering of the cell was left nearly intact (perforated patch), recovery from inactivation (half-time of recovery) in the newborn cells was significantly slower than for the adult cells when either a conditioning potential of Ϫ80 mV (140 Ϯ 9 vs. 58 Ϯ 4 ms, newborn vs. adult; P Ͻ 0.05) or Ϫ50 mV (641 Ϯ 106 vs. 168 Ϯ 15 ms, newborn vs. adult; P Ͻ 0.05) was used. Forskolin significantly increased half-time of recovery for both adult and newborn cells. Dialysis with no calcium buffer showed a slower recovery from inactivation in newborn cells. Intracellular dialysis with a calcium buffer masked differences in recovery from inactivation of I Ca between newborn and adult rabbit ventricular cells. (22) previously reported that the time constant of inactivation (using EGTA with the dialysis-patch technique) was greater in newborn than in adult rabbit ventricular cells, and the same developmental difference has recently been shown to be present with the use of the perforated-patch technique (14).On the other hand, the mechanisms of recovery from inactivation of I Ca are still not well established. The recovery from inactivation is affected by the holding potential, the voltage and duration of the conditioning pulse, the frequency of the coupled pulses, and the extracellular ionic milieu. When I Ca was increased by increasing extracellular [Ca 2ϩ ], by applying ␤-adrenoreceptor agonists or by dialyzing cAMP analogs, the time course of recovery from inactivation was estimated to be faster (28, 29, 31) or slower (3, 11). The reason for this diversity is not well known. These different findings and interpretations concerning recovery from inactivation may result from the use of different voltage-clamp protocols, different solutions, and different species, but the influences of I Ca density, ␤-adrenoreceptor agonist, and extracellular [Ca 2ϩ ] suggest tha...

Age-dependent changes in ion channel mRNA expression in canine cardiac tissues

“…Regarding inward currents, expression of Cav1.2, the pore forming subunit of I Ca-L , together with the corresponding current density, increased with ontogeny in rabbits (Wetzel et al 1991(Wetzel et al , 1993Osaka and Joyner 1991;Huang et al 2006;Namiki et al 2007), guinea pigs (Kato et al 1996), and mice (Davies et al 1996;Liu et al 2002;Harrell et al 2007;Nguemo et al 2009), decreased in rats (Cohen and Lederer 1988), while was not age-dependent in humans (Cohen and Lederer 1993;Roca et al 1996), and dogs (present study). I Ca-T density and Cav3.2 expression was shown to increase with age in rabbits (Wetzel et al 1991) and dogs (present study), decrease in mice (Yasui et al 2005;Harrell et al 2007), while displayed a biphasic change by first increasing then decreasing in rat atrial myocytes (Xu and Best 1992).…”

Dopamine increases L-type calcium current more in newborn than adult rabbit cardiomyocytes via D1 and β2 receptors

“…Under the same conditions, the basal current was 2.6 Ϯ 0.2 pA/pF in the NB, which nearly doubled with dopamine to 4.9 Ϯ 0.4 pA/pF (n ϭ 6, P Ͻ 0.05). The larger basal current in the AD is consistent with our previous studies (35,39). The concentration-dependent effects of dopamine are summarized in Fig.…”

Functional Expression and Inactivation of L-type Ca²⁺ Currents During Murine Heart Development -Implications for Cardiac Ca²⁺ Homeostasis

“…As shown for native cardiac tissue from other species [37], we could recently show that during murine embryonic stem (ES) cell differentiation, the functional expression of I CaL increased from EDS to LDS-derived cardiomyocytes [38]. A detailed analysis of the underlying reasons, however, was missing so far.…”

“…Thus, the acceleration of I CaL inactivation may, at least in part, contribute to the shortening of the AP plateau during development. [1,37,55] can however not be excluded. Also molecular aspects might have contributed to the observed differences.…”