Modulation by pH o and Intracellular Ca 2+ of Na + -H + Exchange in Diabetic Rat Isolated Ventricular Myocytes

1997 ◽  
Vol 80 (2) ◽  
pp. 253-260 ◽  
Author(s):  
Karine Le Prigent ◽  
Dominique Lagadic-Gossmann ◽  
Danielle Feuvray
Keyword(s):  
Ventricular Myocytes ◽  
Diabetic Rat ◽  
Intracellular Ca ◽  
Isolated Ventricular Myocytes

scholarly journals Effects of β-adrenoceptor stimulation on contractility, [Ca2+]i, and Ca2+ current in diabetic rat cardiomyocytes

1998 ◽  
Vol 274 (6) ◽  
pp. H1849-H1857 ◽  
Author(s):  
Atsushi Tamada ◽  
Yuichi Hattori ◽  
Hideki Houzen ◽  
Yoichi Yamada ◽  
Ichiro Sakuma ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Myocytes ◽  
Ventricular Myocytes ◽  
Diabetic Rat ◽  
Inotropic Response ◽  
Dibutyryl Camp ◽  
Rat Cardiomyocytes ◽  
Adrenergic Response ◽  
Significant Difference ◽  
Intracellular Ca

The mechanism of the diminished inotropic response to β-adrenoceptor stimulation in diabetic hearts was studied in enzymatically isolated diabetic rat ventricular myocytes in comparison with age-matched controls. The increases in contractions and intracellular Ca2+ concentration ([Ca2+]i) transients produced by isoproterenol were markedly diminished in diabetic myocytes. The inotropic and [Ca2+]iresponses to forskolin and dibutyryl cAMP (DBcAMP) were also reduced. No significant difference was found in the stimulating effects of isoproterenol, forskolin, and DBcAMP on the L-type Ca2+ current ( I Ca) between control and diabetic myocytes. The rise of [Ca2+]iin response to rapid caffeine application, an index of sarcoplasmic reticulum (SR) Ca2+ content, was significantly decreased in diabetic myocytes. Isoproterenol, forskolin, and DBcAMP enhanced this [Ca2+]iresponse to caffeine in control myocytes more markedly than in diabetic myocytes. The changes in the isoproterenol responses observed in diabetic myocytes were prevented by insulin therapy. We conclude that 1) diabetes causes an impairment of the contractile and [Ca2+]iresponses of cardiac myocytes when stimulated at both β-adrenoceptors and the postreceptor level without affecting the I Ca response and 2) altered SR functions of uptake and/or release of Ca2+ may primarily contribute to the diminished β-adrenergic response.

scholarly journals Increases in diastolic [Ca2+] can contribute to positive inotropy in guinea pig ventricular myocytes in the absence of changes in amplitudes of Ca2+ transients

2006 ◽  
Vol 291 (4) ◽  
pp. H1623-H1634 ◽  
Author(s):  
Robin H. Shutt ◽  
Gregory R. Ferrier ◽  
Susan E. Howlett
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Guinea Pig ◽  
High Resistance ◽  
Ventricular Myocytes ◽  
Edge Detector ◽  
Contraction Amplitude ◽  
Positive Inotropy ◽  
Resting Cell ◽  
Intracellular Ca ◽  
Isolated Ventricular Myocytes

Increases in contraction amplitude following rest or in elevated extracellular Ca2+ concentration ([Ca2+]) have been attributed to increased sarcoplasmic reticulum (SR) Ca2+ stores and/or increased trigger Ca2+. However, either manipulation also may elevate diastolic [Ca2+]. The objective of this study was to determine whether elevation of diastolic [Ca2+] could contribute to positive inotropy in isolated ventricular myocytes. Voltage-clamp experiments were conducted with high-resistance microelectrodes in isolated myocytes at 37°C. Intracellular free [Ca2+] was measured with fura-2, and cell shortening was measured with an edge detector. SR Ca2+ stores were assessed with 10 mM caffeine (0 mM Na+, 0 mM Ca2+). Following a period of rest, cells were activated with trains of pulses, which generated contractions of increasing amplitude, called positive staircases. Positive staircases were accompanied by increasing diastolic [Ca2+] but no change in Ca2+ transient amplitudes. When extracellular [Ca2+] was elevated from 2.0 to 5.0 mM, resting intracellular [Ca2+] increased and resting cell length decreased. Amplitudes of contractions and L-type Ca2+ current increased in elevated extracellular [Ca2+], although SR Ca2+ stores, assessed by rapid application of caffeine, did not increase. Although Ca2+ transient amplitude did not increase in 5.0 mM extracellular [Ca2+], diastolic [Ca2+] continued to increase with increasing extracellular [Ca2+]. These data suggest that increased diastolic [Ca2+] contributes to positive inotropy following rest or with increasing extracellular [Ca2+] in guinea pig ventricular myocytes.

Simulated ischemia-induced preconditioning of isolated ventricular myocytes from young adult and aged Fischer-344 rat hearts

2008 ◽  
Vol 295 (2) ◽  
pp. H768-H777 ◽  
Author(s):  
J. Darcy O'Brien ◽  
Susan E. Howlett
Keyword(s):  
Young Adult ◽  
Ventricular Myocytes ◽  
Contractile Function ◽  
Marked Rise ◽  
Early Reperfusion ◽  
Fischer 344 ◽  
Simulated Ischemia ◽  
Intracellular Ca ◽  
The Impact ◽  
Isolated Ventricular Myocytes

The impact of ischemic preconditioning (IPC) on contraction, Ca2+ homeostasis, and cell survival was compared in isolated ventricular myocytes from young adult (∼3 mo) and aged (∼24 mo) male Fischer-344 rats. Myocytes were field stimulated at 4 Hz (37°C). Contraction (edge detector) and intracellular Ca2+ (fura-2) were measured simultaneously. Viability was assessed with trypan blue. All cells were exposed to 30 min of simulated ischemia followed by reperfusion. Some cells were preconditioned by exposure to 5 min of simulated ischemia before prolonged ischemia. Pretreatment with IPC abolished postischemic contractile depression, inhibited diastolic contracture, and increased Ca2+ transient amplitudes in reperfusion in young adult and aged cells. IPC did not affect the modest rise in diastolic Ca2+ in ischemia in young adult myocytes. However, IPC abolished the marked rise in diastolic Ca2+ observed in ischemia and early reperfusion in aged myocytes. IPC also suppressed mechanical alternans in ischemia in aged cells, but younger myocytes showed little evidence of mechanical alternans whether or not cells were preconditioned. IPC markedly improved cell viability in reperfusion in young adult but not aged cells. These results suggest that IPC augments the recovery of contractile function in reperfusion by increasing Ca2+ transient amplitudes in ventricular myocytes from young adult and aged rats. IPC reduced diastolic Ca2+ accumulation in ischemia in aged myocytes, which may diminish the severity of mechanical alternans in aged cells. Nonetheless, the efficacy of IPC is compromised in aging, as IPC did not improve survival of aged myocytes exposed to ischemia and reperfusion.

Reduced Contraction and Altered Frequency Response of Isolated Ventricular Myocytes From Patients With Heart Failure

Circulation ◽  
1995 ◽  
Vol 92 (9) ◽  
pp. 2540-2549 ◽  
Author(s):  
C.H. Davies ◽  
K. Davia ◽  
J.G. Bennett ◽  
J.R. Pepper ◽  
P.A. Poole-Wilson ◽  
...  
Keyword(s):  
Heart Failure ◽  
Frequency Response ◽  
Ventricular Myocytes ◽  
Patients With Heart Failure ◽  
Isolated Ventricular Myocytes

scholarly journals Cardiac small-conductance calcium-activated potassium channels in health and disease

2021 ◽  
Vol 473 (3) ◽  
pp. 477-489 ◽  
Author(s):  
Xiao-Dong Zhang ◽  
Phung N. Thai ◽  
Deborah K. Lieu ◽  
Nipavan Chiamvimonvat
Keyword(s):  
Ventricular Myocytes ◽  
Pulmonary Veins ◽  
Differential Sensitivity ◽  
Sk Channels ◽  
Sk Channel ◽  
Ventricular Cells ◽  
Intracellular Ca ◽  
Life Threatening ◽  
Health And Disease ◽  
Small Conductance

AbstractSmall-conductance Ca2+-activated K+ (SK, KCa2) channels are encoded by KCNN genes, including KCNN1, 2, and 3. The channels play critical roles in the regulation of cardiac excitability and are gated solely by beat-to-beat changes in intracellular Ca2+. The family of SK channels consists of three members with differential sensitivity to apamin. All three isoforms are expressed in human hearts. Studies over the past two decades have provided evidence to substantiate the pivotal roles of SK channels, not only in healthy heart but also with diseases including atrial fibrillation (AF), ventricular arrhythmia, and heart failure (HF). SK channels are prominently expressed in atrial myocytes and pacemaking cells, compared to ventricular cells. However, the channels are significantly upregulated in ventricular myocytes in HF and pulmonary veins in AF models. Interests in cardiac SK channels are further fueled by recent studies suggesting the possible roles of SK channels in human AF. Therefore, SK channel may represent a novel therapeutic target for atrial arrhythmias. Furthermore, SK channel function is significantly altered by human calmodulin (CaM) mutations, linked to life-threatening arrhythmia syndromes. The current review will summarize recent progress in our understanding of cardiac SK channels and the roles of SK channels in the heart in health and disease.

Testosterone-augmented contractile responses to α1- and β1-adrenoceptor stimulation are associated with increased activities of RyR, SERCA, and NCX in the heart

2009 ◽  
Vol 296 (4) ◽  
pp. C766-C782 ◽  
Author(s):  
Sharon Tsang ◽  
Stanley S. C. Wong ◽  
Song Wu ◽  
Gennadi M. Kravtsov ◽  
Tak-Ming Wong
Keyword(s):  
Ventricular Myocytes ◽  
Left Ventricular ◽  
Contractile Responses ◽  
Adrenoceptor Antagonist ◽  
Cardiac Contractile ◽  
Plasmic Reticulum ◽  
Adrenoceptor Agonist ◽  
Intracellular Ca ◽  
Developed Pressure ◽  
Stimulation Of

We hypothesized that testosterone at physiological levels enhances cardiac contractile responses to stimulation of both α1- and β1-adrenoceptors by increasing Ca2+ release from the sarcoplasmic reticulum (SR) and speedier removal of Ca2+ from cytosol via Ca2+-regulatory proteins. We first determined the left ventricular developed pressure, velocity of contraction and relaxation, and heart rate in perfused hearts isolated from control rats, orchiectomized rats, and orchiectomized rats without and with testosterone replacement (200 μg/100 g body wt) in the presence of norepinephrine (10−7 M), the α1-adrenoceptor agonist phenylephrine (10−6 M), or the nonselective β-adrenoceptor agonist isoprenaline (10−7 M) in the presence of 5 × 10−7 M ICI-118,551, a β2-adrenoceptor antagonist. Next, we determined the amplitudes of intracellular Ca2+ concentration transients induced by electrical stimulation or caffeine, which represent, respectively, Ca2+ release via the ryanodine receptor (RyR) or releasable Ca2+ in the SR, in ventricular myocytes isolated from the three groups of rats. We also measured 45Ca2+ release via the RyR. We then determined the time to 50% decay of both transients, which represents, respectively, Ca2+ reuptake by sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and removal via the sarcolemmal Na+/Ca2+ exchanger (NCX). We correlated Ca2+ removal from the cytosol with activities of SERCA and its regulator phospholamban as well as NCX. The results showed that testosterone at physiological levels enhanced positive inotropic and lusitropic responses to stimulation of α1- and β1-adrenoceptors via the androgen receptor. The increased contractility and speedier relaxation were associated with increased Ca2+ release via the RyR and faster Ca2+ removal out of the cytosol via SERCA and NCX.

Fluid pressure modulates L-type Ca2+ channel via enhancement of Ca2+-induced Ca2+ release in rat ventricular myocytes

2008 ◽  
Vol 294 (4) ◽  
pp. C966-C976 ◽  
Author(s):  
Sunwoo Lee ◽  
Joon-Chul Kim ◽  
Yuhua Li ◽  
Min-Jeong Son ◽  
Sun-Hee Woo
Keyword(s):  
Ventricular Myocytes ◽  
Fluid Pressure ◽  
Inhibitory Effect ◽  
Cellular Mechanism ◽  
Confocal Imaging ◽  
Rat Ventricular Myocytes ◽  
Whole Cell Patch Clamp ◽  
Current Voltage ◽  
Intracellular Ca ◽  
High Concentrations

This study examines whether fluid pressure (FP) modulates the L-type Ca2+ channel in cardiomyocytes and investigates the underlying cellular mechanism(s) involved. A flow of pressurized (∼16 dyn/cm2) fluid, identical to that bathing the myocytes, was applied onto single rat ventricular myocytes using a microperfusion method. The Ca2+ current ( ICa) and cytosolic Ca2+ signals were measured using a whole cell patch-clamp and confocal imaging, respectively. It was found that the FP reversibly suppressed ICa (by 25%) without altering the current-voltage relationships, and it accelerated the inactivation of ICa. The level of ICa suppression by FP depended on the level and duration of pressure. The Ba2+ current through the Ca2+ channel was only slightly decreased by the FP (5%), suggesting an indirect inhibition of the Ca2+ channel during FP stimulation. The cytosolic Ca2+ transients and the basal Ca2+ in field-stimulated ventricular myocytes were significantly increased by the FP. The effects of the FP on the ICa and on the Ca2+ transient were resistant to the stretch-activated channel inhibitors, GsMTx-4 and streptomycin. Dialysis of myocytes with high concentrations of BAPTA, the Ca2+ buffer, eliminated the FP-induced acceleration of ICa inactivation and reduced the inhibitory effect of the FP on ICa by ≈80%. Ryanodine and thapsigargin, abolishing sarcoplasmic reticulum Ca2+ release, eliminated the accelerating effect of FP on the ICa inactivation, and they reduced the inhibitory effect of FP on the ICa. These results suggest that the fluid pressure indirectly suppresses the Ca2+ channel by enhancing the Ca2+-induced intracellular Ca2+ release in rat ventricular myocytes.

Abnormal myocyte Ca2+homeostasis in rabbits with pacing-induced heart failure

1998 ◽  
Vol 275 (4) ◽  
pp. H1441-H1448 ◽  
Author(s):  
Atsushi Yao ◽  
Zhi Su ◽  
Akihiko Nonaka ◽  
Iram Zubair ◽  
Kenneth W. Spitzer ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ventricular Myocytes ◽  
Rnase Protection Assay ◽  
Protection Assay ◽  
Rnase Protection ◽  
Contraction Coupling ◽  
Intracellular Ca ◽  
Rapid Pacing ◽  
Sodium Binding ◽  
The Times

To determine whether there are abnormalities in myocyte excitation-contraction coupling and intracellular Ca2+concentration ([Ca2+]i) homeostasis in pacing-induced heart failure (PF), we measured L-type Ca2+ current ( I Ca,L) and Na+/Ca2+exchanger current ( I Na/Ca) with voltage clamp and measured intracellular Na+ concentration ([Na+]i) and [Ca2+]iwith the use of sodium-binding benzofuran isophthalate (SBFI) and fluo 3 in ventricular myocytes isolated from control and paced rabbits. The peak systolic and diastolic levels and the amplitude of electrically stimulated [Ca2+]itransients (0.25 Hz, extracellular Ca2+ concentration = 1.08 mM) were significantly less in PF myocytes. Also, there was prolongation of the times to peak and decline of [Ca2+]itransients. I Ca,Ldensity was markedly decreased in PF myocytes. I Na/Ca at −40 mV elicited by rapid exposure to 0 Na+ solution with a rapid solution switcher was significantly reduced in PF myocytes, suggesting that the function of the Na+/Ca2+exchanger is impaired in these myocytes. In PF myocytes the decline of the [Ca2+]itransient when the Na+/Ca2+exchanger was abruptly disabled was markedly prolonged compared with the decline in control myocytes, consistent with depressed sarcoplasmic reticulum (SR) Ca2+-ATPase function. RNase protection assay showed decreased levels of Na+/Ca2+exchanger and SR Ca2+-ATPase mRNA in PF hearts, consistent with the function studies. We conclude that the functions of L-type Ca2+channels, Na+/Ca2+exchanger, and SR Ca2+-ATPase are impaired in myocytes from rabbit hearts with failure induced by rapid pacing. These abnormalities result in reduced [Ca2+]itransients and systolic and diastolic dysfunction and appear to account for the abnormal ventricular function observed.

Scaffold topography alters intracellular calcium dynamics in cultured cardiomyocyte networks

2004 ◽  
Vol 287 (3) ◽  
pp. H1276-H1285 ◽  
Author(s):  
Lihong Yin ◽  
Harold Bien ◽  
Emilia Entcheva
Keyword(s):  
Ventricular Myocytes ◽  
Three Dimensional ◽  
Triggered Release ◽  
In Vitro System ◽  
Functional Changes ◽  
Cardiac Electromechanics ◽  
Intracellular Ca ◽  
Intracellular Calcium Dynamics ◽  
Cell Networks

Structural and functional changes ensue in cardiac cell networks when cells are guided by three-dimensional scaffold topography. We report enhanced synchronous pacemaking activity in association with slow diastolic rise in intracellular Ca2+ concentration ([Ca2+]i) in cell networks grown on microgrooved scaffolds. Topography-driven changes in cardiac electromechanics were characterized by the frequency dependence of [Ca2+]i in syncytial structures formed of ventricular myocytes cultured on microgrooved elastic scaffolds (G). Cells were electrically paced at 0.5–5 Hz, and [Ca2+]i was determined using microscale ratiometric (fura 2) fluorescence. Compared with flat (F) controls, the G networks exhibited elevated diastolic [Ca2+]i at higher frequencies, increased systolic [Ca2+]i across the entire frequency range, and steeper restitution of Ca2+ transient half-width ( n = 15 and 7 for G and F, respectively, P < 0.02). Significant differences in the frequency response of force-related parameters were also found, e.g., overall larger total area under the Ca2+ transients and faster adaptation of relaxation time to pacing rate ( P < 0.02). Altered [Ca2+]i dynamics were paralleled by higher occurrence of spontaneous Ca2+ release and increased sarcoplasmic reticulum load ( P < 0.02), indirectly assessed by caffeine-triggered release. Electromechanical instabilities, i.e., Ca2+ and voltage alternans, were more often observed in G samples. Taken together, these findings 1) represent some of the first functional electromechanical data for this in vitro system and 2) demonstrate direct influence of the microstructure on cardiac function and susceptibility to arrhythmias via Ca2+-dependent mechanisms. Overall, our results substantiate the idea of guiding cellular phenotype by cellular microenvironment, e.g., scaffold design in the context of tissue engineering.

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