ATP regulates cardiac Ca 2+ channel activity via a mechanism independent of protein phosphorylation

Yazawa, Kazuto; Kameyama, Asako; Yasui, Kohichiroh; Li, Jinming; Kameyama, Masaki

doi:10.1007/s004240050314

Cited by 36 publications

(40 citation statements)

References 31 publications

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“…The latter mechanism has been shown to operate for K ATP and I Ca regulation (33,35). In our case, neither the non-hydrolysable analogue of ATP AMP-PCP nor GTP prevented the I HERG run-down caused by ATP depletion (Fig.…”

Section: Glycolysis-derived Atp May Be Responsible For Maintaining Thmentioning

confidence: 67%

Impairment of Human Ether-à-Go-Go-related Gene (HERG) K+ Channel Function by Hypoglycemia and Hyperglycemia

Zhang

Han

Wang

et al. 2003

Journal of Biological Chemistry

112

104

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Hyperglycemia and hypoglycemia both can cause prolongation of the Q-T interval and ventricular arrhythmias. Here we studied modulation of human ether-à -gogo-related gene (HERG) K ؉ channel, the major molecular component of delayed rectifier K ؉ current responsible for cardiac repolarization, by glucose in HEK293 cells using whole-cell patch clamp techniques. We found that both hyperglycemia (extracellular glucose concentration Glucose, the primary end product of the digestion of glycogen, is essential for maintaining life activities in organisms. As a major source of metabolic fuel, degradation of glucose via glycolysis and subsequent oxidative phosphorylation generates high energy phosphates to power the biological processes in the cell. Yet, through an exquisitely complex network of control mechanisms, the rate of glucose metabolism is only as great as needed by the organisms. Moreover, glucose also has other regulatory effects on many cellular functions. Either inadequate or excessive glucose can be harmful to the living system. Therefore, the blood glucose level is dynamically controlled. However, under pathological conditions like diabetes, glucose cannot be efficiently utilized, and the blood glucose level rises. When the blood level of glucose is maintained higher than 7 mM, it is considered as hyperglycemia. Diabetes therapy, on the other hand, can lead to an overly low level of blood glucose, which is referred to as hypoglycemia when the level falls below 3 mM.Either hypoglycemia or hyperglycemia can have deleterious effects on the cells. One common feature of electrophysiological alterations caused by both hypoglycemia and hyperglycemia in the heart is prolongation of Q-T interval and the associated ventricular arrhythmias that are presumably responsible for sudden cardiac death in diabetic patients (1-10). However, the ionic mechanisms by which hyperglycemia and hypoglycemia prolong Q-T interval remained unclear, which is at least a part of the reasons why diabetic patients die of mainly cardiac complications.The human either-à -go-go-related gene (HERG) 1 encodes the rapid component of delayed rectifier K ϩ current in the heart, which is the major repolarizing current in the plateau voltage range of cardiac action potentials. HERG K ϩ channels are susceptible to genetic defects and environmental cues, with the consequence being depression of HERG function in most situations (9). Indeed, most of the cases of long Q-T syndrome are ascribed to dysfunction of HERG channels, particularly that induced by therapeutic drugs (13). It is conceivable that HERG alteration might also be involved in the Q-T prolongation induced by hyperglycemia and hypoglycemia. This thought prompted us to carry out a series of experiments to study the effects of glucose on HERG K ϩ channels and the potential mechanisms.

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Section: Glycolysis-derived Atp May Be Responsible For Maintaining Thmentioning

confidence: 67%

Impairment of Human Ether-à-Go-Go-related Gene (HERG) K+ Channel Function by Hypoglycemia and Hyperglycemia

Zhang

Han

Wang

et al. 2003

Journal of Biological Chemistry

112

104

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“…In contrast, the persistent increase requires ATP and, perhaps, ATP-dependent phosphorylation, since the L-type currents ran down within minutes in the presence of NaUTP. ATP has been reported to regulate cardiac L-type channels by phosphorylation-dependent and -independent mechanisms (4,61). Whatever the mechanism, addition of ATP (5-20 mM) to the pipette has been reported to delay Ca 2ϩ channel rundown (28).…”

Section: Discussionmentioning

confidence: 99%

“…Intracellular ATP has been shown to modulate the activity of voltage-activated Ca 2ϩ channels by phosphorylation-dependent and -independent mechanisms (4,61). We compared the effects of MgATP (5 and 10 mM) and UTP (5 mM) on the time-dependent expression of the noninactivating, presumed L-type Ca 2ϩ currents in AZF cells.…”

Section: Voltage-gated Camentioning

confidence: 99%

Adrenal fasciculata cells express T-type and rapidly and slowly activating L-type Ca²⁺channels that regulate cortisol secretion

Enyeart

2015

American Journal of Physiology-Cell Physiology

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Enyeart JJ, Enyeart JA. Adrenal fasciculata cells express T-type and rapidly and slowly activating L-type Ca 2ϩ channels that regulate cortisol secretion. Am J Physiol Cell Physiol 308: C899 -C918, 2015. First published March 18, 2015; doi:10.1152/ajpcell.00002.2015.-In whole cell patch-clamp recordings, we characterized the L-type Ca 2ϩ currents in bovine adrenal zona fasciculata (AZF) cells and explored their role, along with the role of T-type channels, in ACTH-and angiotensin II (ANG II)-stimulated cortisol secretion. Two distinct dihydropyridine-sensitive L-type currents were identified, both of which were activated at relatively hyperpolarized potentials. One activated with rapid kinetics and, in conjunction with Northern blotting and PCR, was determined to be Cav1.3. The other, expressed in approximately one-half of AZF cells, activated with extremely slow voltage-dependent kinetics and combined properties not previously reported for an L-type Ca 2ϩ channel. The T-type Ca 2ϩ channel antagonist 3,5-dichloro-N-[1-(2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-4-fluoro-piperidin-4-ylmethyl]-benzamide (TTA-P2) inhibited Cav3.2 current in these cells, as well as ACTH-and ANG II-stimulated cortisol secretion, at concentrations that did not affect L-type currents. In contrast, nifedipine specifically inhibited L-type currents and cortisol secretion, but less effectively than TTA-P2. Diphenylbutylpiperidine Ca 2ϩ antagonists, including pimozide, penfluridol, and fluspirilene, and the dihydropyridine niguldipine blocked Cav3.2 and L-type currents and inhibited ACTH-stimulated cortisol secretion with similar potency. This study shows that bovine AZF cells express three Ca 2ϩ channels, the voltage-dependent gating and kinetics of which could orchestrate complex mechanisms linking peptide hormone receptors to cortisol secretion through action potentials or sustained depolarization. The function of the novel, slowly activating L-type channel is of particular interest in this respect. Regardless, the well-correlated selective inhibition of T-and L-type currents and ACTH-and ANG II-stimulated cortisol secretion by TTA-P2 and nifedipine establish the critical importance of these channels in AZF cell physiology. adrenal fasciculata; cortisol; ACTH; ANG II; TTA-P2; L-type Ca 2ϩ channel; Cav3.2; Cav1.3 IN MAMMALS, ZONA FASCICULATA cells of the adrenal cortex secrete glucocorticoids in a diurnal rhythm under the control of the pituitary peptide adrenocorticotropic hormone (ACTH) (57). Physical and psychological stress triggers additional bursts of corticosteroid secretion in response to activation of the hypothalamic-pituitary-adrenal axis (57). In some species, including bovine and human, angiotensin II (ANG II) also stimulates glucocorticoid production (10,30,43).Glucocorticoids, including cortisol and corticosterone, regulate a variety of physiological processes, ranging from energy metabolism to long-term memory formation and emotional behavior (8,10,25,32). Chronic excessive cortisol secretion, which occurs in prolonged str...

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“…We used 10 M CSL and 1.22 M CaM, which were submaximum concentrations for the channel-repriming effects, together with 3 mM ATP in all of the inside-out patch experiments. ATP was necessary to induce channel activity (19,22,23). In the previous studies, it has been reported that ATP supports channel activity by a mechanism independent of protein phosphorylation but not fully understood (22,23).…”

Section: Calpastatin Domain L Suppresses Cav12 Channel Activity In Tmentioning

confidence: 99%

Calpastatin Domain L Is a Partial Agonist of the Calmodulin-binding Site for Channel Activation in Cav1.2 Ca2+ Channels

Minobe

Asmara

Saud

et al. 2011

Journal of Biological Chemistry

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Cav1.2 Ca2؉ channel activity diminishes in inside-out patches (run-down). Previously, we have found that with ATP, calpastatin domain L (CSL) and calmodulin (CaM) recover channel activity from the run-down in guinea pig cardiac myocytes. Because the potency of the CSL repriming effect was smaller than that of CaM, we hypothesized that CSL might act as a partial agonist of CaM in the channel-repriming effect. To examine this hypothesis, we investigated the effect of the competitions between CSL and CaM on channel activity and on binding in the channel. We found that CSL suppressed the channel-activating effect of CaM in a reversible and concentration-dependent manner. The channel-inactivating effect of CaM seen at high concentrations of CaM, however, did not seem to be affected by CSL. In the GST pull-down assay, CSL suppressed binding of CaM to GST fusion peptides derived from C-terminal regions in a competitive manner. The inhibition of CaM binding by CSL was observed with the IQ peptide but not the PreIQ peptide, which is the CaM-binding domain in the C terminus. The results are consistent with the hypothesis that CSL competes with CaM as a partial agonist for the site in the IQ domain in the C-terminal region of the Cav1.2 channel, which may be involved in activation of the channel. Calpastatin (CS)2 is a specific endogenous inhibitor of calpain, a Ca 2ϩ -activated cysteine protease. The calpain and CS complex plays a pivotal role in cell adhesion, shape change, migration, and apoptosis. CS is composed of a unique leader domain (domain L) in the N-terminal and four repetitive homologous domains (domains 1-4), each of which has calpain-inhibiting activity. However, CS domain L (CSL) has no calpain-inhibiting activity (1), and its physiological role remains largely unknown. Previous studies have shown that CS or CSL reprimes activity of Cav1.2 Ca 2ϩ channels, in a concentration-dependent manner, in cardiac myocytes using the inside-out patch clamp technique (2, 3). Subsequent studies have further shown that the effective region of CSL is confined to a region spanning 11 amino acid residues (amino acids 54 -64 in exon 5) and that CSL can bind to a fragment derived from the intracellular C-terminal region of Cav1.2 channels (4, 5). However, it has not been clarified how CSL interacts with the channel and regulates its activity.Calmodulin (CaM) is a small (18 kDa), ubiquitous, Ca 2ϩ -binding protein that mediates Ca 2ϩ -dependent regulation of various target proteins, such as enzymes, ion channels, and transporters (6). The activity of the Cav1.2 Ca 2ϩ channel is controlled by Ca 2ϩ -dependent facilitation (CDF) and inactivation (CDI) (7-11). CaM has been suggested to serve as a Ca 2ϩ sensor and a transducer to produce Ca 2ϩ -dependent conformation changes of the channel protein in both CDF and CDI. In the case of CDF, although another mechanism involving phosphorylation of the channels by Ca 2ϩ /CaM-dependent protein kinase has been suggested (12), the activation of the kinase is also mediated by CaM. In our prev...

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ATP regulates cardiac Ca 2+ channel activity via a mechanism independent of protein phosphorylation

Cited by 36 publications

References 31 publications

Impairment of Human Ether-à-Go-Go-related Gene (HERG) K+ Channel Function by Hypoglycemia and Hyperglycemia

Impairment of Human Ether-à-Go-Go-related Gene (HERG) K+ Channel Function by Hypoglycemia and Hyperglycemia

Adrenal fasciculata cells express T-type and rapidly and slowly activating L-type Ca²⁺channels that regulate cortisol secretion

Calpastatin Domain L Is a Partial Agonist of the Calmodulin-binding Site for Channel Activation in Cav1.2 Ca2+ Channels

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ATP regulates cardiac Ca 2+ channel activity via a mechanism independent of protein phosphorylation

Cited by 36 publications

References 31 publications

Impairment of Human Ether-à-Go-Go-related Gene (HERG) K+ Channel Function by Hypoglycemia and Hyperglycemia

Impairment of Human Ether-à-Go-Go-related Gene (HERG) K+ Channel Function by Hypoglycemia and Hyperglycemia

Adrenal fasciculata cells express T-type and rapidly and slowly activating L-type Ca2+channels that regulate cortisol secretion

Calpastatin Domain L Is a Partial Agonist of the Calmodulin-binding Site for Channel Activation in Cav1.2 Ca2+ Channels

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Adrenal fasciculata cells express T-type and rapidly and slowly activating L-type Ca²⁺channels that regulate cortisol secretion