Decreased beating rate variability of spontaneously contracting cardiomyocytes after co-incubation with endotoxin

This study was designed to characterize adenosine's negative chronotropic effect on ventricular pacemakers. The spontaneous beating rate of isolated, isovolumic rat ventricular preparations perfused with Krebs-Henseleit solution decreased as the adenosine concentration was increased [log M effective concentration 50% (EC50) = -5.22 +/- 0.17]. The lack of effect of propranolol or atropine on this adenosine response eliminates the involvement of endogenous neurotransmitters. Support for the involvement of an external cell surface receptor was provided by findings that theophylline and 8-(4-sulfophenyl)theophylline, an analogue thought to act solely at the cell surface, significantly increased the adenosine log M EC50 to -3.94 +/- 0.22 and -3.61 +/- 0.22, respectively. An increase in spontaneous beating rate induced by theophylline, but not by its analogue, was blocked by the addition of propranolol. The relative chronotropic potency of the adenosine analogues R-PIA, S-PIA, and NECA suggests that the cell surface receptors may be of the Ri type. The negative chronotropic effects of adenosine and its analogues occurred at concentrations that had no effect on the developed pressure of the paced preparation. Electrocardiographic evaluations indicate that at high agonist concentrations, there was an abrupt alteration in electrical properties of the preparation, which could be blocked by theophylline and its analogue.

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Antagonistic influences of dibutyryl cyclic AMP and dibutyryl cyclic GMP on the beating rate of cultured mouse myocardial cells

Journal of Molecular and Cellular Cardiology ◽

10.1016/0022-2828(76)90013-4 ◽

1976 ◽

Vol 8 (9) ◽

pp. 713-725 ◽

Cited By ~ 13

Author(s):

K Goshima

Keyword(s):

Cyclic Amp ◽

Cyclic Gmp ◽

Myocardial Cells ◽

Dibutyryl Cyclic Amp ◽

Beating Rate

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On generators of wing beating rate during flight and sound production in some insect species

Journal of Evolutionary Biochemistry and Physiology ◽

10.1134/s0022093011030108 ◽

2011 ◽

Vol 47 (3) ◽

pp. 299-301

Author(s):

P. V. Ozerskii ◽

E. V. Shchekanov

Keyword(s):

Sound Production ◽

Insect Species ◽

Beating Rate

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Effects of extracts ofZanthoxylum fruit and their constituents on spontaneous beating rate of myocardial cell sheets in culture

Phytotherapy Research ◽

10.1002/ptr.2650070111 ◽

1993 ◽

Vol 7 (1) ◽

pp. 41-48 ◽

Cited By ~ 12

Author(s):

Xin-Li Huang ◽

Nobuko Kakiuchi ◽

Qing-Ming Che ◽

Sheng-Lun Huang ◽

Masao Hattori ◽

...

Keyword(s):

Myocardial Cell ◽

Cell Sheets ◽

Beating Rate

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Heat acclimation: cardiac performance of isolated rat heart

Journal of Applied Physiology ◽

10.1152/jappl.1986.60.1.9 ◽

1986 ◽

Vol 60 (1) ◽

pp. 9-13 ◽

Cited By ~ 27

Author(s):

M. Horowitz ◽

Y. Shimoni ◽

S. Parnes ◽

M. S. Gotsman ◽

Y. Hasin

Keyword(s):

Heat Acclimation ◽

Left Ventricular ◽

Isolated Rat Heart ◽

Cardiac Performance ◽

Volume Load ◽

Beating Rate ◽

Maximal Pressure ◽

Lv Volumes ◽

The Right ◽

Perfused Hearts

Cardiac performance was studied in the isolated perfused hearts of rats heat acclimated at 34 degrees C (AC) and their age-matched controls (C). The pressure-volume curves during isovolumetric conditions showed a shift to the right in AC compared with C hearts. At similar left ventricular (LV) volumes end-diastolic and peak systolic pressures of AC hearts were lower, but no difference was observed in the maximal pressure developed at the highest LV volumes measured. In both C and AC hearts the developed force decreased as pacing rate increased. AC and C heart responses were the same up to 250 pulses/min. At higher frequencies the amplitude of the developed force of AC hearts was smaller than that of the controls. In accordance the tension produced by very early premature beat reduced in AC compared with C hearts. Since no hypertrophy was observed in AC hearts, it is concluded that heat acclimation results in a change in the intrinsic properties of the AC hearts exhibited by increased compliance, reduced chamber stiffness, and a decrease in the tension developed for each volume load. It is also suggested that at a high beating rate AC hearts fail to restitute its contractility as quickly as C hearts.

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Decreased beating rate variability of cultured cardiomyocytes by endotoxin

Critical Care ◽

10.1186/cc484 ◽

1999 ◽

Vol 3 (Suppl 1) ◽

pp. P110

Author(s):

H Schmidt ◽

U Müller-Werdan ◽

K Werdan

Keyword(s):

Beating Rate ◽

Cultured Cardiomyocytes

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The relation between the dimensions of the cirral net, the beat frequency and the size and age of the animal in Balanus balanoides and Elminius modestus

Journal of the Marine Biological Association of the United Kingdom ◽

10.1017/s0025315400036547 ◽

1990 ◽

Vol 70 (3) ◽

pp. 505-514 ◽

Cited By ~ 10

Author(s):

D.J. Crisp ◽

F.J. Maclean

Keyword(s):

Correlation Coefficient ◽

Constant Velocity ◽

Maximum Rate ◽

Beat Frequency ◽

Constant Rate ◽

Beating Rate ◽

Balanus Balanoides

The expected allometry between the linear cirral length and animal volume or weight for isometry should be 0·33; similarly the rate of beating, db/dt, might also be expected to increase as −0·33 with volume. The average allometry index of cirral length is less in both Balanus balanoides (0·22–0·23) and in Elminius modestus (0·27–0·32). The segment numbers also rise less than expected.The rate of beat in Balanus balanoides correlates well with size (-0·28) and with temperature with a correlation coefficient of 0·898, significant for both variables. For a group of 11 species the relation between maximum rate of beating and size over 5 decades gives an approximate allometry of −0·24 which is also less than the expected −0·33 for an isometric linear appendage moving at constant velocity. It is suggested that the approximately reciprocal allometry index between cirral beating rate (−0·28) and cirral length (+0·22) may be mutually compensating, resulting in the cirri moving through the water at a constant rate during the growth of the animal. This rate may maximise the chance of prey being captured.

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Age-associated abnormalities of intrinsic automaticity of sinoatrial nodal cells are linked to deficient cAMP-PKA-Ca2+signaling

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00088.2014 ◽

2014 ◽

Vol 306 (10) ◽

pp. H1385-H1397 ◽

Cited By ~ 16

Author(s):

Jie Liu ◽

Syevda Sirenko ◽

Magdalena Juhaszova ◽

Steven J. Sollott ◽

Shweta Shukla ◽

...

Keyword(s):

Heart Rate ◽

Cell Function ◽

Ryanodine Receptors ◽

Phosphodiesterase Inhibitor ◽

Receptor Activation ◽

Functional Changes ◽

Adult Mice ◽

Size Number ◽

Pathway Activation ◽

Beating Rate

A reduced sinoatrial node (SAN) functional reserve underlies the age-associated decline in heart rate acceleration in response to stress. SAN cell function involves an oscillatory coupled-clock system: the sarcoplasmic reticulum (SR), a Ca2+clock, and the electrogenic-sarcolemmal membrane clock. Ca2+-activated-calmodulin-adenylyl cyclase/CaMKII-cAMP/PKA-Ca2+signaling regulated by phosphodiesterase activity drives SAN cells automaticity. SR-generated local calcium releases (LCRs) activate Na+/Ca2+exchanger in the membrane clock, which initiates the action potential (AP). We hypothesize that SAN cell dysfunctions accumulate with age. We found a reduction in single SAN cell AP firing in aged (20–24 mo) vs. adult (3–4 mo) mice. The sensitivity of the SAN beating rate responses to both muscarinic and adrenergic receptor activation becomes decreased in advanced age. Additionally, age-associated coincident dysfunctions occur stemming from compromised clock functions, including a reduced SR Ca2+load and a reduced size, number, and duration of spontaneous LCRs. Moreover, the sensitivity of SAN beating rate to a cAMP stress induced by phosphodiesterase inhibitor is reduced, as are the LCR size, amplitude, and number in SAN cells from aged vs. adult mice. These functional changes coincide with decreased expression of crucial SR Ca2+-cycling proteins, including SR Ca2+-ATPase pump, ryanodine receptors, and Na+/Ca2+exchanger. Thus a deterioration in intrinsic Ca2+clock kinetics in aged SAN cells, due to deficits in intrinsic SR Ca2+cycling and its response to a cAMP-dependent pathway activation, is involved in the age-associated reduction in intrinsic resting AP firing rate, and in the reduction in the acceleration of heart rate during exercise.

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Abstract 11423: Mitochondrial Calcium Flux Modulates Pacemaker Activity in Mouse Stem Cell Derived Cardiomyocytes

Circulation ◽

10.1161/circ.130.suppl_2.11423 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

An Xie ◽

Anyu Zhou ◽

Hong Liu ◽

Guangbin Shi ◽

Kenneth R Boheler ◽

...

Keyword(s):

Ryanodine Receptor ◽

Mrna Level ◽

Embryonic Stem ◽

Calcium Flux ◽

Pacemaker Activity ◽

Receptor Subtypes ◽

Ip3 Receptors ◽

Cell Current ◽

Beating Rate

INTRODUCTION: Ca2+ release from sarcoplasmic reticulum (SR) is known to contribute to the pacemaker activity in embryonic stem cells (ESC) derived cardiomyocytes (CMs). Mitochondria are known to participate in Ca2+ cycling. Nevertheless, the role of mitochondria in pacemaker activity is unclear. We studied the role of mitochondrial Ca2+ flux in spontaneously activity of ESC derived CMs. METHODS: CMs were derived from Wt and ryanodine receptor type 2 knockout (RYR2-/-) mouse ESC. Action potentials (APs) were recorded by perforated whole-cell current-clamp. Cytoplasmic and mitochondrial Ca2+ transients were determined by Fluo-4 and Rhod-2 respectively. Mitochondrial Ca2+ uniporter (MCU) siRNA was used. The mRNA level was evaluated by qPCR. RESULTS: As predicted, SR Ca2+ handling inhibitors, 10 μM ryanodine and 2 μM 2-APB, reduced spontaneous beating rate to 56% and 73% respectively in Wt CMs. Inhibition of mitochondrial Ca2+ flux by 10 μM Ru360 showed a similar inhibition effect on the pacemaker activity as 2 μM 2-APB in Wt CMs. To isolate the mitochondrial component, we used RYR2-/- CMs. In these cells, MCU inhibition by pharmacological or molecular biological means reduced beating rate. The MCU mRNA decreased by 96% after MCU siRNA silence 72 hrs (p<0.01). AP and mitochondrial Ca2+ transient synchronous recording revealed that the reduction of spontaneous beating rate accompanied with the depressed mitochondrial Ca2+ uptaking and releasing. In RyR2-/- CMs, 2 μM 2-APB could significantly lower the spontaneous beating rate. While 2 μM 2-APB was applied to MCU silenced RyR2-/- CMs, the beating rate couldn’t be slowed down further. This indicated IP3 receptors reduced spontaneous beating rate via MCU. Thapsigargin could substantially slow down beating rate like 2-APB. Caffeine depletion experiments showed other ryanodine receptor subtypes didn’t contribute Ca2+ release in RyR2-/- CMs. A L-type Ca2+ channel block, 10 μM nifedipine, couldn’t reduce beating frequency. This indicated spontaneous beating rate is Ca2+ influx independent in RyR2-/- CMs. CONCLUSIONS: Mitochondrial Ca2+ handling plays an important role in decreasing spontaneous beating rate. IP3R reduced spontaneous beating rate through MCU.

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