Subcellular [Ca
            <sup>2+</sup>
            ]
            <sub>i</sub>
            Gradients During Excitation-Contraction Coupling in Newborn Rabbit Ventricular Myocytes

Haddock, Peter; Coetzee, William A.; Cho, Emily; Porter, Lisa M.; Katoh, Hideki; Bers, Donald M.; Jafri, M. Saleet; Artman, Michael

doi:10.1161/01.res.85.5.415

Cited by 156 publications

(152 citation statements)

References 33 publications

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“…In adult, Kir6.2 and SUR2 subunits both are expressed at the sarco- lemma as well as in sarcomeric striated patterns, which we previously attributed to high expression levels of these subunits in t-tubular structures (22). Our observation of predominantly surface expression of Kir6.2 subunits in immature ventricular myocytes is entirely consistent with the fact that neonatal myocytes largely lack t-tubules (30,31). However, we still observe diffuse intracellular staining with the SUR2 antibodies used.…”

Section: Discussionsupporting

confidence: 89%

Expression of ATP-Sensitive K+ Channel Subunits during Perinatal Maturation in the Mouse Heart

et al. 2005

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Prevailing data suggest that sarcolemmal ATP-sensitive (K ATP ) channels in the adult heart consist of Kir6.2 and SUR2A subunits, but the expression of other K ATP channel subunits (including SUR1, SUR2B, and Kir6.1) is poorly defined. The situation is even less clear for the immature heart, which shows a remarkable resistance to hypoxia and metabolic stress. The hypoxia-induced action potential shortening and opening of sarcolemmal K ATP channels that occurs in adults is less prominent in the immature heart. This might be due in part to the different biophysical and pharmacological properties of K ATP channels of immature and adult K ATP channels. Because these properties are largely conferred by subunit composition, it is important to examine the relative expression levels of the various K ATP channel subunits during maturation. We therefore used RNAse protection assays, reverse transcription-PCR approaches, and Western blotting to characterize the mRNA and protein expression profiles of K ATP channel subunits in fetal, neonatal, and adult mouse heart. Our data indicate that each of the K ATP channel subunits (Kir6.1, Kir6.2, SUR1, SUR2A, and SUR2B) is expressed in the mouse heart at all of the developmental time points studied. However, the expression level of each of the subunits is low in the fetal heart and progressively increases with maturation. Each of the subunits seems to be expressed in ventricular myocytes with a subcellular expression pattern matching that found in the adult. Our data suggest that the K ATP channel composition may change during maturation, which has important implications for K ATP channel function in the developing heart. ATP-sensitive K ϩ (K ATP ) channels are robustly expressed in the immature heart (1,2). However, K ATP channels in the immature heart may differ in several respects to those of adult cardiac tissue. In immature rabbit ventricle, K ATP channel open probability is roughly the same as in the adult, but they exhibit a significantly smaller single-channel conductance (~55 pS) and channel density, as defined by the number of open channels per patch (3). In the immature rat heart, K ATP channel density is also high, but the single-channel conductance and the mean open time are the same as in the adult (2). Reports describing a smaller unitary conductance in neonatal rat atrium (4) suggested that there may be regional differences. The immature rat heart K ATP channel has a lower open probability, and the channels are much more sensitive to block by intracellular ATP (2,5). In addition to these biophysical changes, there are reports that immature K ATP channels may have a different pharmacological profile. The neonatal atrial K ATP channel shows a unique functional and pharmacological profile resembling the pancreatic ␤ cell channel for its unusually high affinity for glibenclamide and diazoxide (4,5). These characteristics suggest that neonatal K ATP channels may differ in their molecular composition relative to the mature heart. K ATP channels are believed to be hetero-...

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Section: Discussionsupporting

confidence: 89%

Expression of ATP-Sensitive K+ Channel Subunits during Perinatal Maturation in the Mouse Heart

et al. 2005

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“…causes significant changes in the Ca 2ϩ transient. In addition, the sodium-calcium exchanger has been shown to be larger in newborn rabbit ventricle than adults and may act, in ventricular cells, in the reverse mode to bring Ca 2ϩ into the cell during the plateau of the action potential and thus may be able to act as a trigger SR Ca 2ϩ release (25)(26)(27)(28). Reverse-mode sodiumcalcium exchanger as a trigger for calcium release has been shown in cardiac myocytes from several species (29 -31).…”

Section: Discussionmentioning

confidence: 99%

Calcium Transients in Infant Human Atrial Myocytes

et al. 2005

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Isolated infant human atrial cells have a slower early repolarization than adult human atrial cells. In addition, from room temperature voltage-clamp studies, infant cells have lower basal L-type calcium currents than adult cells. We hypothesized that the slower repolarization increases the calcium transient of infant human atrial cells. Atrial myocytes were enzymatically dissociated from biopsies of human right atrial appendages of infant (3-8 mo) patients who were undergoing open-heart surgery. Intracellular calcium transients were measured with fluorescence microscopy with application of either square waves or action potential waveforms at physiologic temperature. After repetitive application (1 Hz) of 100-ms duration conditioning depolarizations to 10 mV (from Ϫ80 mV), a test pulse of varying duration (⌬T; 2-100 ms) produced smaller transients (expressed as percentage of the last conditioning pulse) at shorter durations (33 Ϯ 7% for ⌬T ϭ 2 ms, 80 Ϯ 4% for ⌬T ϭ 25 ms). The time course and amplitude of the calcium current, which leads via sarcoplasmic reticulum (SR) calcium release to the calcium transient of cardiac cells, depend not only on the properties of the calcium channel but also on the action potential waveform. Changes in the action potential repolarization rate have been shown to have effects to either increase or decrease the net calcium current and the release of calcium from the SR (1-3). In our recent work comparing action potential waveforms and the amplitude and time course of transient outward current in isolated infant versus adult human atrial cells (4), we showed 1) that infant atrial cells had transient outward current that inactivated much more rapidly than adult atrial cells and 2) that infant cells had a much slower early repolarization phase [consistent with previous work on atrial strips (5)]. The time for 30% repolarization from the peak of the action potential (APD 30 ) was 24.4 Ϯ 11.4 ms for infant atrial cells compared with only 3.6 Ϯ 0.4 ms for adult atrial cells. We have also shown that infant cells have a lower basal amplitude of calcium current than do either young adult or older adult atrial cells (6), with peak L-type calcium current (I Ca ) from voltage steps to 10 mV at room temperature being 1.2 Ϯ 0.1 pA/pF for infant cells and 2.6 Ϯ 0.3 pA/pF for adult cells.The lower I Ca (from square wave voltage-clamp studies) and the prolonged early repolarization phase of the infant atrial cells (from current clamp single-cell studies) may be related in a functional sense if the prolongation of the early repolarization served to increase the calcium entry and thus the intracellular calcium transient in infant atrial cells compared with the faster

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“…Seki et al recently observed a significant reduction in the magnitude of Ca 2+ transients in fetal rat myocytes induced by thapsigargin, 23 whereas Haddock et al reported that no Ca 2+ transients in neonatal rabbit ventricular myocytes are inhibited following the addition of thapsigargin. 28 These conflicting findings may be due to differences in methodology and animal species used. It has been reported that cultured myocytes from neonatal rats exhibit an apparent reduction of RyR density, and Ca 2+ signaling during E-C coupling is modified.…”

Section: Contribution Of Serca To Relaxation In Fetal Ventricular Heartmentioning

confidence: 99%

Fetal and Neonatal Development of Ca2+ Transients and Functional Sarcoplasmic Reticulum in Beating Mouse Hearts

Kawamura

Ishiwata

Takizawa

et al. 2010

Circ J

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Background: It is generally accepted that Ca 2+ -induced Ca 2+ release is not the predominant mechanism during embryonic stages. Most studies have been conducted either on primary cultures or acutely isolated cells, in which an apparent reduction of ryanodine receptor density and alterations in the cell shape have been reported. The aim of the present study was to investigate developmental changes in Ca 2+ transients using whole hearts of mouse embryos and neonates. Methods and Results:Fluo-3 fluorescence signals from stimulated whole hearts were detected using a photomultiplier and stored as Ca 2+ transients. The upstroke and decay of Ca 2+ transients became more rapid from the late embryonic stages to the neonatal stage. After thapsigargin application (an inhibitor of the sarcoplasmic Ca 2+ -ATPase [SERCA]), time to 50% relaxation (T50) of Ca 2+ transients was significantly prolonged. There were no significant changes in T50 after Ru360 application (an inhibitor of mitochondrial Ca 2+ uniporter). The rate of increase in the amplitude of Ca 2+ transients after caffeine application became larger during developmental stages.Conclusions: Ca 2+ homeostasis developmentally changes from a slow rise and decay of Ca 2+ transients to rapid kinetics after the mid-embryonic stage. SERCA began to contribute significantly to Ca 2+ homeostasis at early embryonic stages and sarcoplasmic reticulum Ca 2+ contents increased from embryonic to neonatal stages, whereas mitochondrial Ca 2+ uptake did not contribute to Ca 2+ transients on a beat-to-beat basis. (Circ J 2010; 74: 1442 -1450

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Subcellular [Ca ²⁺ ] _i Gradients During Excitation-Contraction Coupling in Newborn Rabbit Ventricular Myocytes

Cited by 156 publications

References 33 publications

Expression of ATP-Sensitive K+ Channel Subunits during Perinatal Maturation in the Mouse Heart

Expression of ATP-Sensitive K+ Channel Subunits during Perinatal Maturation in the Mouse Heart

Calcium Transients in Infant Human Atrial Myocytes

Fetal and Neonatal Development of Ca2+ Transients and Functional Sarcoplasmic Reticulum in Beating Mouse Hearts

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Subcellular [Ca 2+ ] i Gradients During Excitation-Contraction Coupling in Newborn Rabbit Ventricular Myocytes

Cited by 156 publications

References 33 publications

Expression of ATP-Sensitive K+ Channel Subunits during Perinatal Maturation in the Mouse Heart

Expression of ATP-Sensitive K+ Channel Subunits during Perinatal Maturation in the Mouse Heart

Calcium Transients in Infant Human Atrial Myocytes

Fetal and Neonatal Development of Ca2+ Transients and Functional Sarcoplasmic Reticulum in Beating Mouse Hearts

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Product

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Subcellular [Ca ²⁺ ] _i Gradients During Excitation-Contraction Coupling in Newborn Rabbit Ventricular Myocytes