Can Ca entry via Na-Ca exchange directly activate cardiac muscle contraction?

Bers, Donald M.; Christensen, David M.; Nguyen, Trung Xuan

doi:10.1016/s0022-2828(88)80132-9

Cited by 92 publications

(30 citation statements)

References 24 publications

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“…Furthermore, under the present experimental conditions, Ca2+ influx for activation of contraction was directly mediated through the Na+-Ca2+ exchange mechanism, since other sources of Ca2+ for activation of contraction (Ca2+ influx through slow Ca2+ channels and internal Ca2+ release) were blocked by pretreatment with nifedipine and ryanodine. A similar result has been reported by Bers et al (1988). These findings suggest that disopyramide effects the contraction activated through the Na+-Ca2+ exchange mechanism.…”

Section: Discussionsupporting

confidence: 89%

Negative inotropic effects of disopyramide on guinea‐pig papillary muscles

Kondo

Mizukami

Shibata

1990

British J Pharmacology

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The inhibitory effects of disopyramide on electromechanical responses were investigated in guinea‐pig papillary muscles driven by electrical stimuli. Disopyramide up to 10−5 m did not cause a negative inotropic effect, while the maximum upstroke velocity of the action potential (dV/dtmax) was significantly decreased. At higher concentrations, this drug dose‐dependently inhibited the contraction, and dV/dtmax was further decreased. This inhibition of contraction was accompanied by a depression of the slow action potential in partially depolarized preparations by increasing [K+]o (26 mm). In preparations pretreated with nifedipine (10−6 m) and ryanodine (10−6 m), the contraction was almost completely inhibited. In such preparations, ouabain (2 × 10−6 m) markedly increased the contraction, probably through the Na+‐Ca2+ exchange mechanism. This contraction was inhibited by disopyramide above 10−8 m, and an almost complete inhibition was caused at 3 × 10−5 m. A similar inhibitory effect was observed on the contraction increased by the lowering of [Na+]o (36 mm). These results suggest that disopyramide at high concentrations inhibits Ca influx through slow Ca2+ channels and at low concentrations, it reduces the contraction increased through the Na+‐Ca2+ exchange mechanism. Disopyramide had a greater effect on cardiac contractility mediated by the Na+‐Ca2+ exchange mechanism.

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Section: Discussionsupporting

confidence: 89%

Negative inotropic effects of disopyramide on guinea‐pig papillary muscles

Kondo

Mizukami

Shibata

1990

British J Pharmacology

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“…Its capacity to function in the reverse mode, promoting sarcolemmal Ca i 2ϩ entry, has also been described but most conspicuously as a phenomenon during ischemia and reperfusion (23,37,44). Evidence is accumulating, however, that demonstrates that, under basal conditions, the Na ϩ /Ca 2ϩ exchanger may operate in the Ca i 2ϩ influx mode to increase SR Ca i 2ϩ content and contribute to contractility (7,9,26). The lack of consensus on this point may be partly ascribed to the different cell preparations and species studied.…”

Section: Discussionmentioning

confidence: 99%

Enhanced gene expression of Na⁺/Ca²⁺exchanger attenuates ischemic and hypoxic contractile dysfunction

Hampton

Wang

DeAngelis

et al. 2000

American Journal of Physiology-Heart and Circulatory Physiology

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Enhanced gene expression of the Na+/Ca2+exchanger in failing hearts may be a compensatory mechanism to promote influx and efflux of Ca2+, despite impairment of the sarcoplasmic reticulum (SR). To explore this, we monitored intracellular calcium (Cai 2+) and cardiac function in mouse hearts engineered to overexpress the Na+/Ca2+ exchanger and subjected to ischemia and hypoxia, conditions known to impair SR Cai 2+transport and contractility. Although baseline Cai 2+and function were similar between transgenic and wild-type hearts, significant differences were observed during ischemia and hypoxia. During early ischemia, Cai 2+ was preserved in transgenic hearts but significantly altered in wild-type hearts. Transgenic hearts maintained 40% of pressure-generating capacity during early ischemia, whereas wild-type hearts maintained only 25% ( P < 0.01). During hypoxia, neither peak nor diastolic Cai 2+ decreased in transgenic hearts. In contrast, both peak and diastolic Cai 2+ decreased significantly in wild-type hearts. The decline of Cai 2+ was abbreviated in hypoxic transgenic hearts but prolonged in wild-type hearts. Peak systolic pressure decreased by nearly 10% in hypoxic transgenic hearts and >25% in wild-type hearts ( P < 0.001). These data demonstrate that enhanced gene expression of the Na+/Ca2+ exchanger preserves Cai 2+ homeostasis during ischemia and hypoxia, thereby preserving cardiac function in the acutely failing heart.

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“…In fact, calcium influx through the exchanger has been reported to be large enough to induce calcium release from the SR producing contraction. 26 Thus, it is clear that the Na + -Ca 2+ exchanger has the capacity to transport modest amounts of calcium into cardiac cells.…”

Section: Discussionmentioning

confidence: 99%

Calcium dependency of frequency-stimulated atrial natriuretic peptide secretion.

Schiebinger

Cragoe

1994

Hypertension

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In this study we examined the mechanism whereby atrial natriuretic peptide secretion is increased when the frequency of contraction is raised from 2 to 5 Hz. We tested the hypothesis that calcium plays a significant role in the frequency-stimulated response. Using superfused rat left atria, we found that lowering the superfusate calcium concentration from 1.8 to 0.2 mmol/L abolished the frequency-stimulated atrial natriuretic peptide secretory response. Superfusion with ryanodine (1 /xmol/L), an inhibitor of sarcoplasmic reticulum calcium release, resulted in a minimal inhibitory effect. Superfusion with 50 junol/L nitrendipine or 10 junol/L diltiazem inhibited the frequency-stimulated response by 46% to 48%. The lack of total inhibition suggested that an additional mechanism of calcium influx was involved, namely, inward calcium movement carried by Na + -Ca 2+ exchange. As intracellular sodium has been reported to rise with an increase in beat frequency, a fall in the sodium gradient would favor inward calcium movement by Na + -Ca 2+ exchange. Because we could not directly assess the role of Na + -Ca 2+ exchange in this experimental paradigm, we examined the effect of lowering the transmembrane sodium gradient on atrial natriuretic peptide secretion by superfusion with the sodium channel activator A trial tachycardias are associated with a rise in / \ plasma atrial natriuretic peptide (ANP) lev-A.JL els. 15 Using an isolated superfused rat atrial preparation, we have found that increasing the frequency of atrial contraction directly increases ANP secretion 6 ; this observation has been confirmed. 7 In the present study, we examined the mechanisms whereby an increase in the frequency of contraction enhances ANP secretion.It has been reported that raising the contraction frequency increases intracellular sodium activity (a' N> ) in rat atrial muscle. 8 In cardiac tissue, a rise in a' N , results in an increase in cytosolic calcium via Na + -Ca 2+exchange. 910 We therefore tested the hypothesis that calcium plays a significant role in the frequency-stimulated ANP secretory response because we and others have noted that calcium appears to play an important role in stimulated ANP secretion. 1115In addition, we attempted to determine the source of the rise in a' Nt , speculating that an increase in Na + -H + antiporter activity may contribute.

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Can Ca entry via Na-Ca exchange directly activate cardiac muscle contraction?

Cited by 92 publications

References 24 publications

Negative inotropic effects of disopyramide on guinea‐pig papillary muscles

Negative inotropic effects of disopyramide on guinea‐pig papillary muscles

Enhanced gene expression of Na⁺/Ca²⁺exchanger attenuates ischemic and hypoxic contractile dysfunction

Calcium dependency of frequency-stimulated atrial natriuretic peptide secretion.

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Can Ca entry via Na-Ca exchange directly activate cardiac muscle contraction?

Cited by 92 publications

References 24 publications

Negative inotropic effects of disopyramide on guinea‐pig papillary muscles

Negative inotropic effects of disopyramide on guinea‐pig papillary muscles

Enhanced gene expression of Na+/Ca2+exchanger attenuates ischemic and hypoxic contractile dysfunction

Calcium dependency of frequency-stimulated atrial natriuretic peptide secretion.

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Enhanced gene expression of Na⁺/Ca²⁺exchanger attenuates ischemic and hypoxic contractile dysfunction