• Title, Summary, Keyword: $Na^+-Ca^{2+}$ exchange

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Role of $Na^+/Ca^{2+}$ Exchange in the Control of Contractility in Rabbit Basilar Arterial Smooth Muscle

  • Kim, Eui-Yong;Han, Jin
    • The Korean journal of physiology & pharmacology
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    • v.28 no.2
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    • pp.159-167
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    • 1994
  • The contraction of rabbit basilar artery was examined as a function of changes in the $Na^+$ electrochemical gradient in order to determine the contribution of $Na^+/Ca^{2+}$ exchange to the modulation of contractility. Ouabain $(10^{-5}\;M)$ or $K^+-free$ Tyrode solution caused an increase in tonic tension even in the presence of a $Ca^{2+}$ channel blocker $(10^{-6}\;M\;verapamil)$ and an ${\alpha}-receptor$ blocker $(10^{-5}\;M\;phentolamine)$. After treatment with ouabain $(10^{-5}\;M)$, contractions were augmented by reduction of external $Na^+$ concentration. The longer the treatment with ouabain $(10^{-5}\;M)$ was, the larger the amplitude of $Na^+-free$ contracture was. $Na^+-free$ contracture wag induced by either substitution of equimolar Tris for $Na^+$ or substitution of equimolar $Li^+\;for\;Na^+$. The competition between $Na^+\;and\;Ca^{2+}$ for the $Na^+/Ca^{2+}$ exchange carrier would exist, because it was observed that contractility was dependent on the $Na^+$ electrochemical gradient or the extracellular $Ca^{2+}$ concentration (2 mM, 4 mM). Ryanodine $(10^{-7}\;M)$, the blocker of intracellular $Ca^{2+}$ release from the sarcoplasmic reticulum, did not suppress the development of $Na^+-free$ contracture. The contractile response to norepinephrine $(10^{-6}\;M)$ was augmented by reducing the extracellular $Na^+$ concentration. The relaxation rate from caffeine-induced contraction was dependent on the extracellular $Na^+$ concentration (0 mM, 140 mM). From the above results, it could be suggested that $Na^+/Ca^{2+}$ exchange can move $Ca^{2+}$ either into or out of rabbit basilar arterial smooth muscle. $Ca^{2+}$ entry or extrusion is dependent upon the $Na^+$ electrochemical gradient. $Na^+/Ca^{2+}$ exchange plays a significant role in the regulation of contractility in rabbit basilar arterial smooth muscle.

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Increase in $Na^+-Ca^{2+}$ Exchange Activity in Sarcolemma Isolated from Mesenteric Arteries of Spontaneously Hypertensive Rats

  • Lee, Shin-Woong;Lee, Jeung-Soo;Park, Young-Joo;Park, In-Sook
    • Archives of Pharmacal Research
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    • v.12 no.2
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    • pp.128-134
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    • 1989
  • $Na^+-Ca^{2+}$ exchange process in sarcolemmal vesicles isolated from mesenteric arteries of Wistar-Kyoto normotensive(WKY) and spontaneously hypertensive rats(SHR) was investigated. The sarcolemmal fractions isolated after homogenization and sucrose density gradient centrifugation were enriched with 5'-nucleotidase and ouabain sensitive, $K^+-dependent$ phosphatase activities. When the vesicles were loaded with $Na^+$, a time dependent $Ca^{2+}$ uptake was observed. However, very little $Ca^{2+}$ uptake was observed when the vesicles were loaded with $K^+$, or $Ca^{2+}$ uptake of the $Na^+-loaded$ vesicles was carried out in high sodium medium so that there was no sodium gradient. When the vesicles loaded with $Ca^{2+}$ by $Na^+-Ca^{2+}$ exchange were diluted into potassium medium containing EGTA, $Ca^{2+}$ was rapidly released from the vesicles. $Na^+-dependent\;Ca^{2+}$ uptake was increased in SHR compared to WKY, but passive efflux of preaccumulated $Ca^{2+}$ from the vesicles was decreased in SHR. The data indicate that the membrane vesicles of rat mesenteric arteries exhibit $Na^+-Ca^{2+}$ exchange activity. It is also suggested that changes of this process in vascular smooth muscle cell membrane of SHR may be involved in higher intracellular $Ca^{2+}$ concentration and higher basal tone in SHR.

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Effect of sodium on transmembrane calcium movement in the cat ileal longitudinal muscle

  • Rho, Young-Jae;Yun, Il;Kang, Jung-Sook
    • Archives of Pharmacal Research
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    • v.10 no.2
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    • pp.80-87
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    • 1987
  • To get a better insight into the exxistence and the role of a Na-Ca exchange mechanism in smooth muscle, the effect of Na substitution with sucrose on tension development, cellular Ca uptake and $^{45}Ca$ efflux was investigated using isolated cat ileal longitudinal muscle strips. Experimental results were summarized as follows;1) Exposure of the cat ileal longitudinal muscle to Na-free solution induced a contraction, and the magnitude of the contraction increased after incubation of the muscle strips with ouabain ($2{\times10^{-}5}$M) for 1hr. 2) Cellular Ca uptake in Na-free solution increased with an increase in Na content of the Na-loading media, and a linear relationship existed between tissue Na content and cellular Ca uptake for 10 min 3) After tissues were equilibrated in PSS containing $^{45}Ca$ for 2hr, cellular Ca uptake decreased with rising the external Na concentration. 4)Removal of medium Na or inhibition of the Na-K pump decreased the rate of $^{45}Ca$ efflux. These results strongly suggested that Na substitution increases cellular Ca uptake and decreases the rate of $^{45}Ca$ efflux via a Na-Ca exchange mechanism.

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A Study on Na/Ca Exchange Ratio in Atrial Muscle of Rabbit (토끼 심방근 세포막의 Na/Ca교환 비율에 관한 연구)

  • Kim, Eui-Yong;Hwang, Sang-Ik;Earm, Yung-E;Sung, Ho-Kyung
    • The Korean journal of physiology & pharmacology
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    • v.23 no.2
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    • pp.291-299
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    • 1989
  • Na and Ca effects on contracture were studied in order to estimate Na/Ca exchange ratio in the isolated atrial muscle of the rabbit. All experiments were performed in tris-buffered Tyrode solution which was being aerated with 100% $O_2\;and\;kept\;at\;37^{circ}C$. To load intracellular $Na^+,\;10{-6}M$ ouabain or K-free solution were used. Contractures were induced by brier exposure of atrial muscle to Tyrode solution containing various concentrations of Ca or of Na. The results obtained were as follows: 1 ) Increasing the extracellular Ca concentration, the amplitude of contracture also increased and was maximum at 8 mM Ca-Tyrode solution. 2) The relationship between extracellular Ca concentrations and relative amplitude of the contractures showed hyperbolic pattern. By using Hill plot, the line has the slope of 1 12 which means the number of Ca binding sites of the carrier in the cell membrane. 3) The amplitude of the contracture was maximum in 0 mM Na-Tyrode solution and decreased in dose dependent manner when the Na concentration increased. 4) When the relationship between extracellular Na concentrations and the amplitude of contractures was expressed as dose-response curve, the curve showed sigmoid pattern. The line with the slope of 2.82 was obtained by using Hill plot. 5) From above all the results, it is suggested that exchange ratio of Na and Ca via Na/ca exchange system in the atrial muscle of rabbit could be 3:1 approximately.

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Relatoinship between Sarcoplasmic Reticular Calcium Release and $Na^+-Ca^{2+}$ Exchange in the Rat Myocardial Contraction

  • Kim, Eun-Gi;Kim, Soon-Jin;Ko, Chang-Mann
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.3
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    • pp.197-210
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    • 2000
  • Suppressive role of $Na^+-Ca^{2+}$ exchange in myocardial tension generation was examined in the negative frequency-force relationship (FFR) of electric field stimulated left atria (LA) from postnatal developing rat heart and in the whole-cell clamped adult rat ventricular myocytes with high concentration of intracellular $Ca^{2+}$ buffer (14 mM EGTA). LA twitch amplitudes, which were suppressed by cyclopiazonic acid in a postnatal age-dependent manner, elicited frequency-dependent and postnatal age-dependent enhancements after $Na^+-reduced,\;Ca^{2+}-depleted$ (26 Na-0 Ca) buffer application. These enhancements were blocked by caffeine pretreatment with postnatal age-dependent intensities. In the isolated rat ventricular myocytes, stimulation with the voltage protocol roughly mimicked action potential generated a large inward current which was partially blocked by nifedipine or $Na^+$ current inhibition. 0 Ca application suppressed the inward current by $39{\pm}4%$ while the current was further suppressed after 0 Na-0 Ca application by $53{\pm}3%.$ Caffeine increased this inward current by $44{\pm}3%$ in spite of 14 mM EGTA. Finally, the $Na^+$ current-dependent fraction of the inward current was increased in a stimulation frequency-dependent manner. From these results, it is concluded that the $Ca^{2+}$ exit-mode (forward-mode) $Na^+-Ca^{2+}$ exchange suppresses the LA tension by extruding $Ca^{2+}$ out of the cell right after its release from sarcoplasmic reticulum (SR) in a frequency-dependent manner during contraction, resulting in the negative frequency-force relationship in the rat LA.

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Heterogeneity of the SR-dependent Inward $Na^+-Ca^{2+}$ Exchange Current in the Heavily $Ca^{2+}-buffered$ Rat Ventricular Myocytes

  • Yoon, Kyung-Bong;Ahn, Sung-Wan;Ko, Chang-Mann
    • The Korean Journal of Physiology and Pharmacology
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    • v.8 no.2
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    • pp.101-110
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    • 2004
  • Voltage-sensitive release mechanism was pharmacologically dissected from the $Ca^{2+}-induced\;Ca^{2+}\;release$ in the SR $Ca^{2+}$ release in the rat ventricular myocytes patch-clamped in a whole-cell mode. SR $Ca^{2+}$ release process was monitored by using forward-mode $Na^+-Ca^{2+}$ exchange after restriction of the interactions between $Ca^{2+}$ from SR and $Na^+-Ca^{2+}$ exchange within micro-domains with heavy cytosolic $Ca^{2+}$ buffering with 10 mM BAPTA. During stimulation every 10 s with a pulse roughly mimicking action potential, the initial outward current gradually turned into a huge inward current of $-12.9{\pm}0.5\;pA/pF$. From the inward current, two different inward $I_{NCX}s$ were identified. One was $10\;{\mu}M$ ryanodine-sensitive, constituting $14.2{\pm}2.3%$. It was completely blocked by $CdCl_2$ (0.1 mM and 0.5 mM) and by $Na^+-depletion$. The other was identified by 5 mM $NiCl_2$ after suppression of $I_{CaL}$ and ryanodine receptor, constituting $14.8{\pm}1.6%$. This latter was blocked by either 10 mM caffeine-induced SR $Ca^{2+}-depletion$ or 1 mM tetracaine. IV-relationships illustrated that the latter was activated until the peak in $30{\sim}35\;mV$ lower voltages than the former. Overall, it was concluded that the SR $Ca^{2+}$ release process in the rat ventricular myocytes is mediated by the voltage-sensitive release mechanism in addition to the $Ca^{2+}-induced-Ca^{2+}\;release$.

Roles of $Na^+\;-Ca^{2+}$ Exchange in the Negative Force-Frequency Relationship

  • Ko, Chang-Mann;Kim, Soon-Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.6
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    • pp.715-724
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    • 1998
  • Frequency-force relationships (FFR) were studied in electrically field stimulated rat left atria (LA) by reducing the stimulation frequency from resting 3 Hz to test frequencies (0.1-1 Hz) for 5 minutes. The twitch amplitudes of LA elicited the typical negative staircases with 3-phased changes: the initial rapid increase, the second decrease and the following plateau at test frequencies. Verapamil $(3{\times}10^{-5}\;M)$ pretreatment elicited frequency-dependent suppression of the twitch amplitudes, exaggerating the negative staircase. Monensin pretreatment enhanced not the peak but the plateau amplitudes in a concentration-dependent manner. When the $Na^+-Ca^{2+}$ exchange was blocked by $Na^+\;and\;Ca^{2+}$ depletion in the Krebs Hensleit buffer (0 $Na^+-0\;Ca^{2+}$ KHB), the twitch amplitudes increased in a frequency-dependent manner, changing the negtive staircase into the positve one. Meanwhile, the 0 $Na^+-0\;Ca^{2+}$ KHB applicationinduced enhancement was strongly suppressed by caffeine (5 mM) pretreatment. Only dibucaine among the local anesthetics increased the basal tone during frequency reduciton. There were no differences in $^{45}Ca$ uptakes between 0.3 Hz and 3 Hz stimulation except at 1 min when it was significantly low at 0.3 Hz than 3 Hz, illustrating net $Ca^{2+}$ losses. Monensin pretreatment enhanced the rate of this $Ca^{2+}$ loss. Taken together, it is concluded that $Na^+-Ca^{2+}$ exchange extrudes more SR released $Ca^{2+}$ out of the cell in proportion to the frequency, resulting in the negative rate staircase in the rat LA.

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A Study on the $Na^+/Ca^{2+}$ Exchange Mechanism in the Smooth Muscle of Guinea-pig Stomach

  • Kim, Eui-Yong;Han, Jin;Kim, Ki-Whan
    • The Korean journal of physiology & pharmacology
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    • v.26 no.1
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    • pp.55-68
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    • 1992
  • The effects of changes in extracellular $Na^+\;and\;Ca^+$ concentration on the membrane potential and contractility were studied in the antral circular muscle of guinea pig stomach in order to elucidate the existence and the nature of $Na^+/Ca^{2+}$ exchange mechanism. All experiments were performed in tris buffered Tyrode solution which was aerated with 100% $O_2$ and kept at $35^{\circ}C.$ The treatment of $10^{-5}$ ouabain was performed to induce intracellular $Na^+$ loading prior to the start of experiment. The results were as follows: 1. $Na^+$-free Tyrode or high $Ca^{2+}$-Tyrode solution hyperpolarized the membrane potential and induced contracture. The time course of contracture was similar to that of change in membrane potential. 2. The degree of hyperpolarization and the amplitude of contracture decreased in accordance with the increase of extracellular $Na^+$ concentration. 3. $Na^+$-free contracture was developed even after blocking the influence of intrinsic nerves by the pretreatment with atropine, guanethidine and TTX. 4. $Ca^{2+}$-channel blockers(D-600 or $Mn^{2+}$) and the blocker of intracellular $Ca^{2+}$ release from sarcoplasmic reticulum(ryanodine) did not suppress the development of $Na^+$-free contracture. And also, dinitrophenol had no effect on $Na^+$-free contracture. 5. Dose-response relationship between extracellular $Na^+$ concentrations and the magnitude of contractures showed a sigmoid pattern. The slope of straight line from Hill plot was 2.7. 6. In parallel with the increase of extracellular $Ca^{2+}$ concentration, the amplitude of contracture increased dose dependently and was maximum at 8 mM $Ca^{2+}$-Tyrode solution. 7. The relationship between extracellular $Ca^{2+}$ concentrations and the magnitude of contractures showed hyperbolic pattern. The slope of straight line from Hill plot was 1.1. From the above results, it is suggested that $Na^+/Ca^{2+}$ exchange mechanism exists in the antral circular muscle of guinea pig stomach and this mechanism affects the membrane potential electrogenically.

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Influences of Divalent Cations and Membrane Phosphorylation Inhibitors on $Na^+-Ca^{++}$ Exchange in Synaptosomes (이가 양이온과 세포막 인산화 반응의 억제제가 Synaptosome에서의 소듐-칼슘 교환이동에 미치는 영향)

  • Shin, Yong-Kyoo;Lee, Chung-Soo;Lee, Kwang-Soo
    • The Korean Journal of Pharmacology
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    • v.24 no.2
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    • pp.179-187
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    • 1988
  • Verapamil, tetrodotoxin and tetraethylammonium chloride in the stated amount did not affect the $Na^{++}$ induced $Ca^{++}$ release. $Cd^{++}$ and $Zn^{++}$ significantly inhibited the $Na^{++}$ induced $Ca^{++}$ release. $Mn^{++}$ also inhibited $Na^+-Ca^{++}$ exchange. $Cd^{++}$ inhibited $Na^+-Ca^{++}$ exchange noncompetitively with an apparent inhibition constant (Ki) of $100\;{\mu}M$. $Cd^{++}$ caused loss of sulfhydryl group, whereas $Zn^{++}$ did not show any significant effect. $Cd^{++}$ and $Zn^{++}$ effectively inhibited $Na^+-Ca^{++}$ ATPase and slightly inhibited $Ca^{++}-Mg^{++}$ ATPase. Carbonyl cyanide chlorophenylhydrazone, 2,4-dinitrophenol and sodium arsenate stimulated the $Na^{++}$ induced $Ca^{++}$ release. Dibucaine and oligomycin slightly inhibited it. The results suggest that the $Na^+-Ca^{++}$ exchange on the synaptosomal plasma membrane may be not accomplished by ion channels. The $Na^+-Ca^{++}$ exchange is sensitively inhibited by $Cd^{++}$ and this transport process appears to be partially regulated by sulfhydryl groups of the synaptosomal plasma membrane. It is also postulated that $Na^+-Ca^{++}$ exchange is suppressed during the phosphorylation reaction of protein component on the neuronal membrane.

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Mechanism of $Ca^{2+}$ Regulation in Osteoblast-like Cells (골아세포내 $Ca^{2+}$ 활성도의 조절기전)

  • Park, Mi-Jung
    • Journal of Korean Biological Nursing Science
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    • v.1 no.1
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    • pp.25-41
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    • 1999
  • Physiological activity of osteoblast including bone formation is known to be closely related to the increase of intracellular $Ca^{2+}$ activity($[Ca^{2+}]_i$) in osteoblast. $Ca^{2+}$ is an important intracellular messenger in diverse cellular functions, and regulation of its level is mediated by the transmembrane $Ca^{2+}$ movement via $Ca^{2+}$ channels, $Na^+-Ca^{2+}$ exchange, and by intracellular $Ca^{2+}$ movement through the intracellular stores. The purpose of this study is to investigate how the intracellular $Ca^{2+}$ is regulated in osteoblast-like cells(OLCs) by measuring $Ca^{2+}$ activity with cell imaging technique. OLCs were isolated from femur and tibia of neonatal rats, and cultured for 7 days. Cultured OLCs were loaded with a $Ca^{2+}$-sensitive fluorescent dye, Fura-2, and fluorescence images were monitored with a cooled CCD camera. The images were processed and analyzed with an image analyzing software. The results were as follows. (1) $[Ca^{2+}]_i$ of OLC decreased as the $Ca^{2+}$ concentration in the superfusing Tyrode solution was lowered. When $Na^+$ concentration in the superfusing solution was decreased, $[Ca^{2+}]_i$ increased.. These suggest that $Ca^{2+}$ flux occurs via the $Na^+-Ca^{2+}$ exchange mechanism. (2) When $Na^+$ in the superfusing solution was removed. a transient $Ca^{2+}$, increase($Ca^{2+}$ spike) was occasionally observed. However, $Ca^{2+}$ spike was not observed after adding 1 ${\mu}M$ thapsigargin. This implies that the generation of $Ca^{2+}$ spike is mediated by the release of $Ca^{2+}$ from endoplasmic reticulum(ER). (3) As the $Ca^{2+}$ concentration in the superfusing solution was raised, the frequency of 0mM $Na^+$-induced $Ca^{2+}$ spike increased, suggesting that $Ca^{2+}$-induced $Ca^{2+}$ release(CICR) mechanism exists. (4) After $[Ca^{2+}]_i$ was decreased with the superfusion of $Ca^{2+}$-free solution containing thapsigargin, the recovery of $[Ca^{2+}]_i$ with reperfusion of 2.5mM $Ca^{2+}$ solution transiently exceeded the control level, suggesting that the depletion of $Ca^{2+}$ in ER induces $Ca^{2+}$ influx from extracellular medium via store-operated $Ca^{2+}$ influx(SOCI) mechanism. (5) $[Ca^{2+}]_i$ was not affected by the superfusion of 25mM $K^+$ Tyrode solution. These results suggest that intracellular $Ca^{2+}$ activity in osteoblast is regulated by transmembrane $Ca^{2+}$ flux via $Na^+-Ca^{2+}$ exchange, $Ca^{2+}$ release from the internal store (ER) via $Ca^{2+}$-induced $Ca^{2+}$ release, and store-operated $Ca^{2+}$ influx across the cell membrane.

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