scholarly journals Differential responses of rabbit ventricular and atrial transient outward current (Ito) to the Itomodulator NS5806

2017 ◽  
Vol 5 (5) ◽  
pp. e13172 ◽  
Author(s):  
Hongwei Cheng ◽  
Mark B. Cannell ◽  
Jules C. Hancox
Keyword(s):  
Outward Current ◽  
Transient Outward Current ◽  
Differential Responses

Regional Differences in Transient Outward Current Density and Inhomogeneities of Repolarization in Rabbit Right Atrium

Circulation ◽  
1995 ◽  
Vol 92 (10) ◽  
pp. 3061-3069 ◽  
Author(s):  
Takeshi Yamashita ◽  
Toshiaki Nakajima ◽  
Hisanori Hazama ◽  
Eiji Hamada ◽  
Yuji Murakawa ◽  
...  
Keyword(s):  
Current Density ◽  
Right Atrium ◽  
Regional Differences ◽  
Outward Current ◽  
Transient Outward Current

scholarly journals Endurance exercise training normalizes repolarization and calcium-handling abnormalities, preventing ventricular fibrillation in a model of sudden cardiac death

2012 ◽  
Vol 113 (11) ◽  
pp. 1772-1783 ◽  
Author(s):  
Ingrid M. Bonilla ◽  
Andriy E. Belevych ◽  
Arun Sridhar ◽  
Yoshinori Nishijima ◽  
Hsiang-Ting Ho ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Exercise Training ◽  
Endurance Exercise ◽  
Cardiac Death ◽  
Outward Current ◽  
Calcium Handling ◽  
Transient Outward Current ◽  
Cellular Electrophysiology ◽  
Endurance Exercise Training

The risk of sudden cardiac death is increased following myocardial infarction. Exercise training reduces arrhythmia susceptibility, but the mechanism is unknown. We used a canine model of sudden cardiac death (healed infarction, with ventricular tachyarrhythmias induced by an exercise plus ischemia test, VF+); we previously reported that endurance exercise training was antiarrhythmic in this model (Billman GE. Am J Physiol Heart Circ Physiol 297: H1171–H1193, 2009). A total of 41 VF+ animals were studied, after random assignment to 10 wk of endurance exercise training (EET; n = 21) or a matched sedentary period ( n = 20). Following (>1 wk) the final attempted arrhythmia induction, isolated myocytes were used to test the hypotheses that the endurance exercise-induced antiarrhythmic effects resulted from normalization of cellular electrophysiology and/or normalization of calcium handling. EET prevented VF and shortened in vivo repolarization ( P < 0.05). EET normalized action potential duration and variability compared with the sedentary group. EET resulted in a further decrement in transient outward current compared with the sedentary VF+ group ( P < 0.05). Sedentary VF+ dogs had a significant reduction in repolarizing K+ current, which was restored by exercise training ( P < 0.05). Compared with controls, myocytes from the sedentary VF+ group displayed calcium alternans, increased calcium spark frequency, and increased phosphorylation of S2814 on ryanodine receptor 2. These abnormalities in intracellular calcium handling were attenuated by exercise training ( P < 0.05). Exercise training prevented ischemically induced VF, in association with a combination of beneficial effects on cellular electrophysiology and calcium handling.

Alpha 1-adrenoceptor subtypes mediating inotropic and electrophysiological effects in mammalian myocardium

1996 ◽  
Vol 271 (4) ◽  
pp. H1423-H1432
Author(s):  
M. Nagashima ◽  
Y. Hattori ◽  
Y. Akaishi ◽  
N. Tohse ◽  
I. Sakuma ◽  
...  
Keyword(s):  
Positive Inotropic Effect ◽  
Outward Current ◽  
Ventricular Myocardium ◽  
Inotropic Effect ◽  
Transient Outward Current ◽  
Papillary Muscles ◽  
Binding Studies ◽  
Positive Inotropism ◽  
Wb 4101 ◽  
Rabbit Ventricular Myocardium

Stimulation of alpha 1-adrenoceptors produces a positive inotropic effect in rat and rabbit ventricular myocardium via different mechanisms, the prolongation of action potential duration (APD) exclusively in the former and an increase in myofibrillar Ca2+ sensitivity in large part in the latter. This study was designed to determine whether the two inotropic mechanisms are mediated by different alpha 1-adrenoceptor subtypes. In rat papillary muscles, the positive inotropic effect and APD prolongation induced by phenylephrine (in the presence of propranolol) were inhibited by WB-4101, but not affected by chlorethylclonidine (CEC). WB-4101, but not CEC, blocked the phenylephrine-induced inhibition of the transient outward current (Ito) in rat ventricular cells. On the other hand, WB-4101 and CEC each antagonized the positive inotropic effect of phenylephrine in rabbit papillary muscles. However, the phenylephrine-induced APD prolongation observed in rabbit papillary muscles was blocked only by WB-4101. These results indicate that the WB-4101 sensitive alpha 1-adrenoceptor subtype mediates the positive inotropism that is correlated with the APD prolongation resulting from Ito reduction, whereas the CEC-sensitive subtype mediates the positive inotropism that is probably associated with increased myofibrillar Ca2+ sensitivity. Radioligand binding studies with [3H] prazosin showed a similar ratio of alpha 1A-to alpha 1B-adrenoceptor subtypes in rat and rabbit ventricular myocardium, implying that the different degree of contribution of each action mechanism to the overall inotropic effect in the two species cannot be explained by distribution of the alpha 1-adrenoceptor subtypes.

A Slow Transient Potassium Current Expressed in a Subset of Neurosecretory Neurons of the Hypothalamic Paraventricular Nucleus

2000 ◽  
Vol 84 (4) ◽  
pp. 1814-1825 ◽  
Author(s):  
Jason A. Luther ◽  
Katalin Cs. Halmos ◽  
Jeffrey G. Tasker
Keyword(s):  
Paraventricular Nucleus ◽  
Potassium Current ◽  
Outward Current ◽  
Retrograde Transport ◽  
Neurosecretory Cells ◽  
Firing Frequency ◽  
Hypothalamic Paraventricular Nucleus ◽  
Transient Outward Current ◽  
Type I ◽  
Double Labeling

Type I putative magnocellular neurosecretory cells of the hypothalamic paraventricular nucleus (PVN) express a prominent transient outward rectification generated by an A-type potassium current. Described here is a slow transient outward current that alters cell excitability and firing frequency in a subset of type I PVN neurons (38%). Unlike most of the type I neurons (62%), the transient outward current in these cells was composed of two kinetically separable current components, a fast activating, fast inactivating component, resembling an A-type potassium current, and a slowly activating [10–90% rise time: 20.4 ± 12.8 (SE) ms], slowly inactivating component (time constant of inactivation: τ = 239.0 ± 66.1 ms). The voltage dependence of activation and inactivation and the sensitivity to block by 4-aminopyridine (5 mM) and tetraethylammonium chloride (10 mM) of the fast and slow components were similar. Compared to the other type I neurons, the neurons that expressed the slow transient outward current were less excitable when hyperpolarized, requiring larger current injections to elicit an action potential (58.5 ± 13.2 vs. 15.4 ± 2.4 pA; 250-ms duration; P < 0.01), displaying a longer delay to the first spike (184.9 ± 15.7 vs. 89.7 ± 8.8 ms with 250- to 1,000-ms, 50-pA current pulses; P < 0.01), and firing at a lower frequency (18.7 ± 4.6 vs. 37.0 ± 5.5 Hz with 100-pA current injections; P < 0.05). These data suggest that a distinct subset of type I PVN neurons express a novel slow transient outward current that leads to a lower excitability. Based on double labeling following retrograde transport of systemically administered fluoro-gold and intracellular injection of biocytin, these cells are neurosecretory and are similar morphologically to magnocellular neurosecretory cells, although it remains to be determined whether they are magnocellular neurons.

I(to) and action potential notch are smaller in left vs. right canine ventricular epicardium

1996 ◽  
Vol 271 (2) ◽  
pp. H548-H561 ◽  
Author(s):  
J. M. Di Diego ◽  
Z. Q. Sun ◽  
C. Antzelevitch
Keyword(s):  
Action Potential ◽  
Phase 1 ◽  
Outward Current ◽  
Disulfonic Acid ◽  
Transient Outward Current ◽  
Pharmacological Agents ◽  
Whole Cell Patch Clamp ◽  
Chloride Channel Blocker ◽  
The Right ◽  
Basic Cycle Length

Transmural heterogeneities of repolarizing currents underlie prominent differences in the electrophysiology and pharmacology of ventricular epicardial, endocardial, and M cells in a number of species. The degree to which heterogeneities exist between the right and left ventricles is not well appreciated. The present study uses standard microelectrode and whole cell patch-clamp techniques to contrast the electrophysiological characteristics and pharmacological responsiveness of tissues and myocytes isolated from right (RVE) and left canine ventricular epicardium (LVE). RVE and LVE studied under nearly identical conditions displayed major differences in the early repolarizing phases of the action potential. The magnitude of phase 1 in RVE was nearly threefold that in LVE: 28.7 +/- 6.2 vs. 10.6 +/- 4.1 mV (basic cycle length = 2,000 ms). Phase 1 in RVE was also more sensitive to alterations of the stimulation rate and to 4-aminopyridine (4-AP), suggesting a much greater contribution of the transient outward current (I(to) 1) in RVE than in LVE. The combination of 4-AP plus ryanodine, low chloride, or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (chloride channel blocker) completely eliminated the notch and all rate dependence of the early phases of the action potential, making RVE and LVE indistinguishable. At +70 mV, RVE myocytes displayed peak I(to) 1 densities between 28 and 37 pA/pF. LVE myocytes included cells with similar I(to) 1 densities (thought to represent subsurface cells) but also cells with much smaller current levels (thought to represent surface cells). Average peak I(to) 1 density was significantly smaller in LVE than in RVE at voltages more than or equal to +10 mV. Our data point to prominent differences in the magnitude of the I(to) 1-mediated action potential notch in cells at the surface of RVE compared with the LVE and suggest that important distinctions may exist in the response of these two tissues to pharmacological agents and pathophysiological states, as previously demonstrated for epicardium and endocardium. Our findings also suggest that a calcium-activated outward current contributes to the early repolarization phase in RVE and LVE and that the influence of this current, although small, is more important in the left ventricle.

scholarly journals Charge Movement Associated with the Opening and Closing of the Activation Gates of the Na Channels

1974 ◽  
Vol 63 (5) ◽  
pp. 533-552 ◽  
Author(s):  
Clay M. Armstrong ◽  
Francisco Bezanilla
Keyword(s):  
Time Course ◽  
Sodium Current ◽  
Close Association ◽  
Outward Current ◽  
Transient Outward Current ◽  
Activation Process ◽  
Charge Movement ◽  
Gating Current ◽  
Dipolar Molecules ◽  
Opening And Closing

The sodium current (INa) that develops after step depolarization of a voltage clamped squid axon is preceded by a transient outward current that is closely associated with the opening of the activation gates of the Na pores. This "gating current" is best seen when permeant ions (Na and K) are replaced by relatively impermeant ones, and when the linear portion of capacitative current is eliminated by adding current from positive steps to that from exactly equal negative ones. During opening of the Na pores gating current is outward, and as the pores close there is an inward tail of current that decays with approximately the same time-course as INa recorded in Na-containing medium. Both outward and inward gating current are unaffected by tetrodotoxin (TTX). Gating current is capacitative in origin, the result of relatively slow reorientation of charged or dipolar molecules in a suddenly altered membrane field. Close association with the Na activation process is clear from the time-course of gating current, and from the fact that three procedures that reversibly block INa also block gating current: internal perfusion with Zn2+, prolonged depolarization of the membrane, and inactivation of INa with a short positive prepulse.

Electrophysiological properties of neurons within the nucleus ambiguus of adult guinea pigs

1991 ◽  
Vol 66 (3) ◽  
pp. 744-761 ◽  
Author(s):  
S. M. Johnson ◽  
P. A. Getting
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Outward Current ◽  
Nucleus Ambiguus ◽  
Transient Outward Current ◽  
Maximum Magnitude ◽  
Action Potential Firing ◽  
Onset Of Action ◽  
Electrophysiological Properties ◽  
Single Action

1. The purpose of this study was to determine the electrophysiological properties of neurons within the region of the nucleus ambiguus (NA), an area that contains the ventral respiratory group. By the use of an in vitro brain stem slice preparation, intracellular recordings from neurons in this region (to be referred to as NA neurons, n = 235) revealed the following properties: postinhibitory rebound (PIR), delayed excitation (DE), adaptation, and posttetanic hyperpolarization (PTH). NA neurons were separated into three groups on the basis of their expression of PIR and DE: PIR cells (58%), DE cells (31%), and Non cells (10%). Non cells expressed neither PIR nor DE and no cells expressed both PIR and DE. 2. PIR was a transient depolarization that produced a single action potential or a burst of action potentials when the cell was released from hyperpolarization. In the presence of tetrodotoxin (TTX), the maximum magnitude of PIR was 7-12 mV. Under voltage-clamp conditions, hyperpolarizing voltage steps elicited a small inward current during the hyperpolarization and a small inward tail current on release from hyperpolarization. These currents, which mediate PIR, were most likely due to Q-current because they were blocked with extracellular cesium and were insensitive to barium. 3. DE was a delay in the onset of action potential firing when cells were hyperpolarized before application of depolarizing current. When cells were hyperpolarized to -90 mV for greater than or equal to 300 ms, maximum delays ranged from 150 to 450 ms. The transient outward current underlying DE was presumed to be A-current because of the current's activation and inactivation characteristics and its elimination by 4-aminopyridine (4-AP). 4. Adaptation was examined by applying depolarizing current for 2.0 s and measuring the frequency of evoked action potentials. Although there was a large degree of variability in the degree of adaptation, PIR cells tended to express less adaptation than DE and Non cells. Nearly three-fourths of all NA neurons adapted rapidly (i.e., 50% adaptation in less than 200 ms), but PIR cells tended to adapt faster than DE and Non cells. PTH after a train of action potentials was relatively rare and occurred more often in DE cells (43%) and Non cells (33%) than in PIR cells (13%). PTH had a magnitude of up to 18 mV and time constants that reflected the presence of one (1.7 +/- 1.4 s, mean +/- SD) or two components (0.28 +/- 0.13 and 4.1 +/- 2.2 s).(ABSTRACT TRUNCATED AT 400 WORDS)

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