β-Adrenergic stimulation does not activate Na+/Ca2+ exchange current in guinea pig, mouse, and rat ventricular myocytes

2006 ◽  
Vol 290 (2) ◽  
pp. C601-C608 ◽  
Author(s):  
Xue Lin ◽  
Hikari Jo ◽  
Yutaka Sakakibara ◽  
Keiichi Tambara ◽  
Bongju Kim ◽  
...  

The effect of β-adrenergic stimulation on cardiac Na+/Ca2+ exchange has been controversial. To clarify the effect, we measured Na+/Ca2+ exchange current ( INCX) in voltage-clamped guinea pig, mouse, and rat ventricular cells. When INCX was defined as a 5 mM Ni2+-sensitive current in guinea pig ventricular myocytes, 1 μM isoproterenol apparently augmented INCX by ∼32%. However, this increase was probably due to contamination of the cAMP-dependent Cl− current (CFTR-Cl− current, ICFTR-Cl), because Ni2+ inhibited the activation of ICFTR-Cl by 1 μM isoproterenol with a half-maximum concentration of 0.5 mM under conditions where INCX was suppressed. Five or ten millimolar Ni2+ did not inhibit ICFTR-Cl activated by 10 μM forskolin, an activator of adenylate cyclase, suggesting that Ni2+ acted upstream of adenylate cyclase in the β-adrenergic signaling pathway. Furthermore, in a low-extracellular Cl− bath solution, 1 μM isoproterenol did not significantly alter the amplitude of Ni2+-sensitive INCX at +50 mV, which is close to the reversal potential of ICFTR-Cl. No change in INCX amplitude was induced by 10 μM forskolin. When INCX was activated by extracellular Ca2+, it was not significantly affected by 1 μM isoproterenol in guinea pig, mouse, or rat ventricular cells. We concluded that β-adrenergic stimulation does not have significant effects on INCX in guinea pig, mouse, or rat ventricular myocytes.

2002 ◽  
Vol 136 (3) ◽  
pp. 361-366 ◽  
Author(s):  
Yasuhide Watanabe ◽  
Takahiro Iwamoto ◽  
Munekazu Shigekawa ◽  
Junko Kimura

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Enio R Vasques ◽  
Helena Nader ◽  
Ivarne Tersariol ◽  
Godoy Carlos

Background: Ion channels are pharmacological targets for antiarrhythmic action, and drugs currently used for this purpose are generally not specific to a site of action and may act on several channels and even trigger proarrhythmic phenomena. Trisulfate disaccharide (TD) is an heparin fragment known to act on the sodium calcium exchanger (NCX), reducing intracellular calcium in overload situations and reversing arrhytmias, but its action on other ionic currents is unknown. Objective: To evaluate by patch clamp the action of TD at different concentrations in NCX and ionic currents in situations of intracellular calcium overload. Materials and Methods: Adult rat myocytes were obtained from a sample from ventricles. Currents were measured using the whole-cell variant of the patch clamp method. Creation of voltage clamp pulses and data acquisition was controlled by a computer with pClamp software. Peak inward current amplitude was measured for ion currents. For Na/Ca exchange current a ramp voltage protocol was employed. Three different concentrations of Cai (300nM, 400nM and 600nM) were used in separate experiments. One drug concentration was applied per cell (10, 30 and 100 micromolar each). The current sensitive to 5mM nickel was taken as the Na/Ca exchange current. The effects of TD on the INa, L-type Ca, and the potassium currents, transiente outward current (Ito), inwardly rectifying potassium current (IK1), and sustained current (Isus) recorded from adult rat ventricular myocytes were also examined in the same conditions. Results: TD concentration-dependently increased the inward Na/Ca exchange current in all intracellular calcium concentration. The effects of TD on the INa, L-type Ca, and the potassium currents, Ito, IK1 and Isus was associated with less than 30% mean reduction on any current at the highest concentration of TD tested (100 micromolar) and still below the positive block controls for different channels that is above 40% block. Conclusion: TD acts on NCX under different concentrations used, without affecting other ionic currents, suggesting specificity in the mechanism of action and possibly not exerting a pro-arrhythmic activity, this effect being desirable for its possible use in reversal of cardiac arrhythmias.


2012 ◽  
Vol 120 (1) ◽  
pp. 59-62 ◽  
Author(s):  
Tomomi Yamakawa ◽  
Yasuhide Watanabe ◽  
Hiroshi Watanabe ◽  
Junko Kimura

1995 ◽  
Vol 269 (3) ◽  
pp. H1165-H1170 ◽  
Author(s):  
J. R. Berlin

Spatial and temporal changes of intracellular calcium ion concentration ([Ca2+]i) during stimulated contractions were observed by confocal microscopy in rat ventricular and guinea pig atrial myocytes. Fluorescence intensity profiles in fluo 3-acetoxymethyl ester (fluo 3-AM)-loaded cells were collected from the entire cell, selected regions of the cell, or along a single scanned line across the cell. In rat ventricular myocytes, the increase of [Ca2+]i after a single stimulus from field electrodes occurred synchronously across the cell whether fluo 3 fluorescence was monitored in a narrow region aligned with the long axis of the cell or in line-scan images of a single z-line across the cell. However, during the onset of Ca2+ channel blockade by nifedipine (5 microM), electrical stimulation produced spatially nonuniform, focal increases of [Ca2+]i. In guinea pig atrial myocytes, stimulated increases of [Ca2+]i first appeared in focal regions at the cell periphery before spreading to the cell interior. Line-scan images showed the peripheral rise of [Ca2+]i led that at the center of the cell by 34 +/- 4 ms (mean +/- SE, n = 3). These data demonstrate that the t-tubular network ensures synchronous increases of [Ca2+]i throughout the cell during an action potential. In the absence of t tubules or when the number of sarcolemmal Ca2+ channels opened by membrane depolarization is greatly reduced, stimulated increases of [Ca2+]i can be observed to arise in focal regions of the cell.


2001 ◽  
Vol 132 (6) ◽  
pp. 1317-1325 ◽  
Author(s):  
Yasuhide Watanabe ◽  
Takahiro Iwamoto ◽  
Isao Matsuoka ◽  
Satoko Ohkubo ◽  
Tomoyuki Ono ◽  
...  

2000 ◽  
Vol 529 (3) ◽  
pp. 611-623 ◽  
Author(s):  
Yasutada Fujioka ◽  
Koh Hiroe ◽  
Satoshi Matsuoka

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