Na+-Ca2+ exchange contributes to increase of cytosolic Ca2+ concentration during depolarization in heart muscle

The possible role of Na+-Ca2+ exchange in contributing to depolarization-induced increase in cytosolic Ca2+ concentration ([Ca2+]i) of isolated rat ventricular myocytes was investigated. Measured with the Ca2+-sensitive indicator quin 2, [Ca2+]i increased from 177 +/- 12 (mean +/- SE, n = 11) to 468 +/- 41 nM when cells were depolarized with solutions containing 50 mM KCl [high extracellular K+ concentration ([K+]o)]. Approximately 73% of this high-[K+]o-induced increase in [Ca2+]i was abolished by the Ca2+ channel blocker verapamil (5 microM). For cells pretreated with 10 mM caffeine to deplete the Ca2+ stored in sarcoplasmic reticulum, 50 mM KCl still produced an increase in [Ca2+]i, even in the presence of 5 microM verapamil. However, if extracellular Na+ was replaced by Li+ or tris(hydroxymethyl)aminomethane, this increase was completely abolished. The results suggest that, in addition to voltage-sensitive Ca2+ channels, voltage-sensitive Na+-Ca2+ exchange can also contribute to the increase in [Ca2+]i on depolarization. Therefore both Ca2+ transport systems may play important roles in regulating cardiac excitation and contraction.

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Characteristic of the vasorlaxant action of the talatisamine alkaloid and its derivatives

Pharmaceutics and Pharmacology Research ◽

10.31579/2693-7247/0/27 ◽

2021 ◽

Vol 4 (2) ◽

pp. 01-05

Author(s):

Mirzayeva Yu.T.

Keyword(s):

Sarcoplasmic Reticulum ◽

Channel Blocker ◽

Aortic Ring ◽

Diterpenoid Alkaloids ◽

Relaxant Effect ◽

Ring Contraction ◽

Voltage Dependent ◽

Ca2 Channels ◽

Isolated Rat

The aim of our research is to study the effect relaxant action of diterpenoid alkaloids talatisamine, 14-O-benzoylthalatisamine and 14-O-acetylthalatisamine was studied using isolated rat aortic rings. Alkaloids significantly and dose-dependently inhibited contraction of the aortic rings caused by high KCl content. At the same time, under these conditions, alkaloids significantly reduced Ca2+-induced contraction of the aortic rings. The relaxing effects of alkaloids are significantly suppressed by verapamil, a potent potentiometer-dependent Ca2+ channel blocker. The alkaloids also significantly reduced norepinephrine-induced aortic ring contraction in normal as well as Ca2+ free Krebs solutions. The data obtained indicate that talatisamine, 14-benzoylthalatisamine and 14-O-acetylthalatisamine exhibit a pronounced relaxant effect in almost the same way in the case of contraction induced by a high content of KCl and norepinephrine. The mechanism of the relaxant action of alkaloids is probably complex and may include suppression of Ca2+influx through voltage-dependent and receptor-driven Ca2+ channels, as well as inhibition of Ca2+transport in the sarcoplasmic reticulum.

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Ca2+ homeostasis and fast-type sarcoplasmic reticulum Ca2+-ATPase expression in L6 muscle cells. Role of thyroid hormone

Biochemical Journal ◽

10.1042/bj2830713 ◽

1992 ◽

Vol 283 (3) ◽

pp. 713-718 ◽

Cited By ~ 6

Author(s):

A Muller ◽

C van Hardeveld ◽

W S Simonides ◽

J van Rijn

Keyword(s):

Thyroid Hormone ◽

Sarcoplasmic Reticulum ◽

Resting Cells ◽

Mediating Role ◽

L6 Myotubes ◽

High K ◽

Control Myotubes ◽

The Mean ◽

K Concentration

The effect of thyroid hormone (L-tri-iodothyronine; T3) on the cytosolic free Ca2+ concentration ([Ca2+]i) in L6 myotubes was studied at rest and during activation to explore the possible mediating role of [Ca2+]i in the T3-induced net synthesis of fast-type sarcoplasmic reticulum (SR) Ca(2+)-ATPase. The mean [Ca2+]i at rest was approx. 115 nM in myoblasts, control myotubes and T3-treated myotubes. Therefore it is unlikely that the T3-induced elevation of Ca(2+)-ATPase levels is mediated by [Ca2+]i changes. To investigate the influence of the 4-fold higher Ca(2+)-ATPase levels in T3-treated myotubes (compared with controls) on [Ca2+]i, interventions with caffeine (10 mM) and a high extracellular K+ concentration ([K+]o) (30 mM) were applied which initially mobilize Ca2+ predominantly from the SR. The results showed a lower (caffeine) or not significantly different (high [K+]o) increase in [Ca2+]i in T3-treated myotubes compared with controls. No rise in [Ca2+]i was found in myoblasts with caffeine or high [K+]o. The role of [Ca2+]i in the regulation of Ca(2+)-ATPase levels was investigated by varying [Ca2+]i through exposure of cells to different concentrations of extracellular Ca2+ (0.2-1.8 mM) and ionomycin (0.1-0.25 microM). At subnormal [Ca2+]i (55 nM) the T3-induced net synthesis of Ca(2+)-ATPase was virtually abolished, and at supranormal [Ca2+]i (195 nM) it was greatly depressed. Intermediate stimulation of net Ca(2+)-ATPase synthesis was found at [Ca2+]i of 95 and 165 nM, with an optimum at approx. 125 nM. Similar but less pronounced effects were found for the basal Ca(2+)-ATPase levels. In contracting primary rat myotubes, Ca(2+)-ATPase levels were significantly lower than in tetrodotoxin-arrested myotubes. The same results were obtained in the presence of T3. Since the mean [Ca2+]i in contracting cells is higher than in resting cells, these data agree with those obtained in the L6 cells with ionomycin. A major conclusion of this study is the existence of a [Ca2+]i optimum, near resting levels, for the expression of the fast-type Ca(2+)-ATPase in the L6 muscle cell line.

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Characteristic of the vasorlaxant action of the talatisamine alkaloid and its derivatives

Pharmaceutics and Pharmacology Research ◽

10.31579/2693-7247/027 ◽

2021 ◽

Vol 4 (2) ◽

pp. 01-05

Author(s):

Mirzayeva Yu.T

Keyword(s):

Sarcoplasmic Reticulum ◽

Channel Blocker ◽

Aortic Ring ◽

Diterpenoid Alkaloids ◽

Relaxant Effect ◽

Ring Contraction ◽

Voltage Dependent ◽

Ca2 Channels ◽

Isolated Rat

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Role of local Ca2+ domains in activation of Ca(2+)-induced Ca2+ release in crayfish muscle fibers

AJP Cell Physiology ◽

10.1152/ajpcell.1993.264.6.c1505 ◽

1993 ◽

Vol 264 (6) ◽

pp. C1505-C1512 ◽

Cited By ~ 21

Author(s):

S. Gyorke ◽

P. Palade

Keyword(s):

Sarcoplasmic Reticulum ◽

Cardiac Muscle ◽

Binding Site ◽

Equal Access ◽

Crayfish Muscle ◽

Simultaneous Measurements ◽

Indicator Analysis ◽

Dependent Processes ◽

Ca2 Channels

Simultaneous measurements were made of crayfish muscle Ca2+ currents (ICa) and the intracellular Ca2+ transients they elicit due to Ca(2+)-induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR). Ca2+ concentration ([Ca2+]) elevations produced by Ca2+ entry via ICa were much more effective in triggering CICR than were ongoing release or homogeneous elevations of Ca2+ produced by photolysis of caged Ca2+. This suggests that [Ca2+] gradients exist when Ca2+ is elevated by ICa and that, during Ca2+ entry, [Ca2+] at the activation site of the release channels must be much greater than spatially averaged [Ca2+] reported by the indicator. Analysis of voltage dependencies of ICa inactivation and SR Ca2+ release suggest that both Ca(2+)-dependent processes are controlled by ICa via the nearest T tubule Ca2+ channel rather than by total ICa entry. The contribution of SR Ca2+ release to ICa inactivation studied with a two-pulse protocol was less than predicted if Ca2+ derived from SR Ca2+ release and from T tubule Ca2+ channels have equal access to the Ca2+ binding site controlling ICa inactivation. These results can be explained in terms of a scheme where sites for release activation and ICa inactivation are located in the same junctional gap subdomain, closer to the cytoplasmic mouth of the T tubule Ca2+ channel than to the cytoplasmic mouth of the SR Ca2+ release channels. Such a scheme could provide an explanation for the graded nature and selective control of CICR in this preparation as well as in vertebrate cardiac muscle.

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Different contributions of L- and Q-type Ca2+ channels to Ca2+ signals and secretion in chromaffin cell subtypes

AJP Cell Physiology ◽

10.1152/ajpcell.1997.272.2.c476 ◽

1997 ◽

Vol 272 (2) ◽

pp. C476-C484 ◽

Cited By ~ 63

Author(s):

R. B. Lomax ◽

P. Michelena ◽

L. Nunez ◽

J. Garcia-Sancho ◽

A. G. Garcia ◽

...

Keyword(s):

Chromaffin Cells ◽

Chromaffin Cell ◽

Channel Blocker ◽

Cell Types ◽

Bay K 8644 ◽

High K ◽

Voltage Dependent ◽

Bovine Chromaffin Cells ◽

P Type ◽

Ca2 Channels

In this study, we investigated the contribution of different subtypes of voltage-dependent Ca2+ channels to changes in cytosolic free Ca2+ ([Ca2+]i) and secretion in noradrenergic and adrenergic bovine chromaffin cells. In single immunocytochemically identified chromaffin cells, [Ca2+]i increased transiently during high K+ depolarization. Furnidipine and BAY K 8644, L-type Ca2+ channel blocker and activator, respectively, affected the [Ca2+]i rise more in noradrenergic than in adrenergic cells. In contrast, the Q-type Ca2+ channel blocker omega-conotoxin MVIIC inhibited the [Ca2+]i rise more in adrenergic cells. omega-Agatoxin IVA (30 nM), which blocks P-type Ca2+ channels, had little effect on the [Ca2+]i signal. The N-type Ca2+ channel blocker omega-conotoxin GVIA similarly inhibited the [Ca2+]i rise in both cell types. The effects of furnidipine, BAY K 8644, and omega-conotoxin MVIIC on K+-evoked norepinephrine and epinephrine release paralleled those effects on [Ca2+]i signals. However, omega-conotoxin GVIA and 30 nM omega-agatoxin IVA did not affect the secretion of either amine. The data suggest that, in the bovine adrenal medulla, the release of epinephrine and norepinephrine are preferentially controlled by Q- and L-type Ca2+ channels, respectively. P- and N-type Ca2+ channels do not seem to control the secretion of either catecholamine.

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Effects of Mg2+ on Ca2+ waves and Ca2+ transients of rat ventricular myocytes

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.270.3.h907 ◽

1996 ◽

Vol 270 (3) ◽

pp. H907-H914 ◽

Cited By ~ 1

Author(s):

H. Terada ◽

H. Hayashi ◽

N. Noda ◽

H. Satoh ◽

H. Katoh ◽

...

Keyword(s):

Sarcoplasmic Reticulum ◽

Channel Blocker ◽

Ventricular Myocytes ◽

Inhibitory Effect ◽

Antiarrhythmic Action ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Triggered Activity ◽

Rat Ventricular Myocytes ◽

High Concentrations

It has been shown that the occurrence of the transient inward current, which is responsible for triggered activity, was often associated with propagating regions of increased intracellular Ca2+ concentration ([Ca2+]i), i.e., the “Ca2+ wave.” To investigate the mechanism of antiarrhythmic action of Mg2+, we have studied effects of high concentrations of Mg2+ on Ca2+ waves in isolated rat ventricular myocytes. [Ca2+]i was estimated using the Ca(2+)-indicating probe indo 1. Ca2+ waves in myocytes, stimulated at 0.2 Hz, were induced by perfusion of isoproterenol (10(-7) M). High Mg2+ concentration suppressed Ca2+ waves in a concentration-dependent manner (36% at 4 mM, 70% at 8 mM, and 82% at 12 mM). The Ca2+ channel blocker verapamil also suppressed Ca2+ waves in a similar way. In contrast with marked depression of Ca2+ transients by verapamil, Ca2+ transients were not affected by high Mg2+ concentration (8 mM). High Mg2+ concentration also reduced frequencies of Ca2+ waves in the absence of electrical stimulation, whereas verapamil failed to reduce frequencies of Ca2+ waves. Reduction in frequency of Ca2+ waves by high Mg2+ concentration was associated with slowing of propagation velocity of Ca2+ waves. To examine whether suppressive effects of high Mg2+ concentration on Ca2+ waves were related to an increase in intracellular Mg2+ concentration ([Mg2+]i), the effect of high-Mg2+ solution on [Mg2+]i was examined in myocytes loaded with mag-fura 2. An increase in extracellular Mg2+ concentration from 1 to 12 mM increased [Mg2+]i from 1.06 +/- 0.16 to 1.87 +/- 0.22 mM (P < 0.01) in 30 min. To examine the effect of high Mg2+ concentration on amount of releasable Ca2+ in the sarcoplasmic reticulum, the effect of high Mg2+ concentration on the Ca2+ transient induced by a rapid application of caffeine was examined. High-Mg2+ solution increased the peak of the caffeine-induced Ca2+ transient. These results suggest that the inhibitory effect of Mg2+ on Ca2+ waves was not due to inhibition of the sarcolemmal Ca2+ channel but could be due to a decreased propensity for the sarcoplasmic reticulum to divest itself of excess Ca2+.

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Stimulation of prolactin release by dopamine withdrawal: role of membrane hyperpolarization

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1994.267.5.e781 ◽

1994 ◽

Vol 267 (5) ◽

pp. E781-E788 ◽

Cited By ~ 3

Author(s):

K. A. Gregerson ◽

N. Golesorkhi ◽

R. Chuknyiska

Keyword(s):

Resting Membrane Potential ◽

Prolactin Release ◽

Membrane Hyperpolarization ◽

Basal Release ◽

K Concentration ◽

Hypothalamic Dopamine ◽

Ca2 Channels ◽

Stimulation Of ◽

External K

Hypothalamic dopamine (DA) tonically inhibits prolactin (PRL) release from the anterior pituitary gland, whereas removal of DA markedly augments its release to values exceeding pre-DA rates. We investigated whether electrical events induced by DA contribute to this secretory rebound. In primary cultured lactotropes, spontaneous Ca(2+)-dependent spiking activity was enhanced after recovery from DA-induced hyperpolarization. Voltage clamp studies showed a rapidly and a slowly inactivating Ca2+ current that were both augmented by a hyperpolarizing conditioning potential. We measured PRL release from perifused cells exposed to DA to correlate the electrical with the secretory responses. DA inhibited PRL release by 67%, whereas PRL secretion increased three- to fourfold over basal release after washout of DA. Valinomycin, used to directly hyperpolarize the cell membrane, mimicked the actions of DA, inhibiting PRL release (65%) and, upon washout, augmenting PRL secretion. Blocking the DA- or valinomycin-induced hyperpolarization by elevating external K+ concentration blocked both the inhibition and rebound of PRL release. These novel results demonstrate that hyperpolarization of the lactotrope membrane by DA is critical for the development of PRL rebound after DA withdrawal. We hypothesize the mechanism involves the removal of inactivation from a population of Ca2+ channels, leading to enhanced Ca2+ influx and PRL release upon recovery of the resting membrane potential after DA removal.

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The calcium stored in the sarcoplasmic reticulum acts as a safety mechanism in rainbow trout heart

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00127.2014 ◽

2014 ◽

Vol 307 (12) ◽

pp. R1493-R1501 ◽

Cited By ~ 12

Author(s):

Caroline Cros ◽

Laurent Sallé ◽

Daniel E. Warren ◽

Holly A. Shiels ◽

Fabien Brette

Keyword(s):

Rainbow Trout ◽

Sarcoplasmic Reticulum ◽

Ventricular Myocytes ◽

Adrenergic Stimulation ◽

Relative Contribution ◽

Safety Mechanism ◽

Rapid Changes ◽

Intracellular Ca ◽

As Stress

Cardiomyocyte contraction depends on rapid changes in intracellular Ca2+. In mammals, Ca2+ influx as L-type Ca2+ current ( ICa) triggers the release of Ca2+ from sarcoplasmic reticulum (SR) and Ca2+-induced Ca2+ release (CICR) is critical for excitation-contraction coupling. In fish, the relative contribution of external and internal Ca2+ is unclear. Here, we characterized the role of ICa to trigger SR Ca2+ release in rainbow trout ventricular myocytes using ICa regulation by Ca2+ as an index of CICR. ICa was recorded with a slow (EGTA) or fast (BAPTA) Ca2+ chelator in control and isoproterenol conditions. In the absence of β-adrenergic stimulation, the rate of ICa inactivation was not significantly different in EGTA and BAPTA (27.1 ± 1.8 vs. 30.3 ± 2.4 ms), whereas with isoproterenol (1 μM), inactivation was significantly faster with EGTA (11.6 ± 1.7 vs. 27.3 ± 1.6 ms). When barium was the charge carrier, inactivation was significantly slower in both conditions (61.9 ± 6.1 vs. 68.0 ± 8.7 ms, control, isoproterenol). Quantification revealed that without isoproterenol, only 39% of ICa inactivation was due to Ca2+, while with isoproterenol, inactivation was Ca2+-dependent (∼65%) and highly reliant on SR Ca2+ (∼46%). Thus, SR Ca2+ is not released in basal conditions, and ICa is the main trigger of contraction, whereas during a stress response, SR Ca2+ is an important source of cytosolic Ca2+. This was not attributed to differences in SR Ca2+ load because caffeine-induced transients were not different in both conditions. Therefore, Ca2+ stored in SR of trout cardiomyocytes may act as a safety mechanism, allowing greater contraction when higher contractility is required, such as stress or exercise.

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Antagonistic Actions of Halothane and Sevoflurane on Spontaneous Ca2+Release in Rat Ventricular Myocytes

Anesthesiology ◽

10.1097/00000542-200607000-00013 ◽

2006 ◽

Vol 105 (1) ◽

pp. 58-64 ◽

Cited By ~ 8

Author(s):

Mark D. Graham ◽

Philip M. Hopkins ◽

Simon M. Harrison

Keyword(s):

Sarcoplasmic Reticulum ◽

Positive Inotropic Effect ◽

Ventricular Myocytes ◽

Inotropic Effect ◽

Release Process ◽

Rat Ventricular Myocytes ◽

Fura 2 ◽

Threefold Increase ◽

Subcellular Target ◽

Isolated Rat

Background Halothane has been reported to sensitize Ca(2+) release from the sarcoplasmic reticulum (SR), which is thought to contribute to its initial positive inotropic effect. However, little is known about whether isoflurane or sevoflurane affect the SR Ca(2+) release process, which may contribute to the inotropic profile of these anesthetics. Methods Mild Ca(2+) overload was induced in isolated rat ventricular myocytes by increase of extracellular Ca(2+) to 2 mM. The resultant Ca(2+) transients due to spontaneous Ca(2+) release from the SR were detected optically (fura-2). Cells were exposed to 0.6 mM anesthetic for a period of 4 min, and the frequency and amplitude of spontaneous Ca(2+) transients were measured. Results Halothane caused a temporary threefold increase in frequency and decreased the amplitude (to 54% of control) of spontaneous Ca(2+) transients. Removal of halothane inhibited spontaneous Ca release before it returned to control. In contrast, sevoflurane initially inhibited frequency of Ca(2+) release (to 10% of control), whereas its removal induced a burst of spontaneous Ca(2+) release. Isoflurane had no significant effect on either frequency or amplitude of spontaneous Ca(2+) release on application or removal. Sevoflurane was able to ameliorate the effects of halothane on the frequency and amplitude of spontaneous Ca(2+) release both on application and wash-off. Conclusions Application of halothane and removal of sevoflurane sensitize the SR Ca(2+) release process (and vice versa on removal). Sevoflurane reversed the effects of halothane, suggesting they may act at the same subcellular target on the SR.

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