β-Adrenergic modulation of L-type Ca2+-channel currents in early-stage embryonic mouse heart

1999 ◽  
Vol 276 (2) ◽  
pp. H608-H613 ◽  
Author(s):  
Weiran Liu ◽  
Kenji Yasui ◽  
Akiko Arai ◽  
Kaichiro Kamiya ◽  
Jianhua Cheng ◽  
...  
Keyword(s):  
Action Potential ◽  
Ventricular Myocytes ◽  
Early Stage ◽  
Cell Voltage ◽  
Mouse Heart ◽  
Embryonic Mouse ◽  
Adrenergic Modulation ◽  
Beating Rate ◽  
Β Adrenergic Receptors ◽  
Channel Currents

Little information is available concerning the modulation of cardiac function by β-adrenergic agonists in early-stage embryonic mammalian heart. We have examined the effects of isoproterenol (Iso) on the spontaneous beating rate and action potential (AP) configuration in embryonic mouse hearts at 9.5 days postcoitum (dpc), just 1 day after they started to beat. Iso (3 μM) increased the spontaneous beating rate in whole hearts, dissected ventricles, and isolated ventricular myocytes. In ventricular myocytes, Iso also increased the slope of the pacemaker potential and the action potential duration but decreased the maximum upstroke velocity. In whole cell voltage-clamp experiments, the Ca2+-channel currents were measured as Ba2+ currents ( I Ba). In 9.5-dpc myocytes, I Ba was enhanced significantly from −4.7 ± 0.9 to −6.7 ± 1.2 pA/pF (by 52.4 ± 14.8%, n = 10) after the application of Iso. Propranolol (3 μM) reversed the effect of Iso. Forskolin (For, 10 μM) produced an increase in I Ba by 95.5 ± 18.8% ( n = 8). In ventricular myocytes at a late embryonic stage (18 dpc), 3 μM Iso caused an appreciably greater increase in I Ba from −6.2 ± 0.5 to −14.5 ± 2.2 pA/pF (by 137.8 ± 33.0%, n = 8), whereas the increase in I Ba by 10 μM For (by 120.0 ± 23.0%, n = 7) was comparable to that observed in the early stage (9.5 dpc). These results indicate that the L-type Ca2+-channel currents are modulated by β-adrenergic receptors in the embryonic mouse heart as early as 9.5 dpc, probably via a cAMP-dependent pathway.

scholarly journals Stretch-activated whole cell currents in adult rat cardiac myocytes

2000 ◽  
Vol 278 (2) ◽  
pp. H548-H557 ◽  
Author(s):  
Tao Zeng ◽  
Glenna C. L. Bett ◽  
Frederick Sachs
Keyword(s):  
Single Channel ◽  
Ventricular Myocytes ◽  
Reversal Potential ◽  
Cell Voltage ◽  
Cellular Level ◽  
Whole Cell ◽  
Adult Rat ◽  
Longitudinal Stretch ◽  
Single Channel Currents ◽  
Channel Currents

Mechanoelectric transduction can initiate cardiac arrhythmias. To examine the origins of this effect at the cellular level, we made whole cell voltage-clamp recordings from acutely isolated rat ventricular myocytes under controlled strain. Longitudinal stretch elicited noninactivating inward cationic currents that increased the action potential duration. These stretch-activated currents could be blocked by 100 μM Gd3+ but not by octanol. The current-voltage relationship was nearly linear, with a reversal potential of approximately −6 mV in normal Tyrode solution. Current density varied with sarcomere length (SL) according to I (pA/pF) = 8.3 − 5.0SL (μm). Repeated attempts to record single channel currents from stretch-activated ion channels failed, in accord with the absence of such data from the literature. The inability to record single channel currents may be a result of channels being located on internal membranes such as the T tubules or, possibly, inactivation of the channels by the mechanics of patch formation.

Identification and characteristics of delayed rectifier K+ current in fetal mouse ventricular myocytes

1996 ◽  
Vol 270 (6) ◽  
pp. H2088-H2093 ◽  
Author(s):  
L. Wang ◽  
H. J. Duff
Keyword(s):  
Action Potential ◽  
Cardiac Myocytes ◽  
Ventricular Myocytes ◽  
Dominant Role ◽  
Ventricular Myocardium ◽  
Negative Slope ◽  
Delayed Rectifier ◽  
Mouse Heart ◽  
Fetal Mouse ◽  
K Current

Although the genetics of mammalian cardiac K+ channels have been most intensively investigated in mice, there are limited data available from the electrophysiological studies of the K+ currents in native mouse cardiac myocytes, especially in fetal mouse heart. The present study utilized whole cell patch-clamp techniques to assess the delayed rectifier K+ current (IK) in fetal (18th day of gestation) mouse ventricular myocytes. IK in fetal mouse ventricular myocytes activated rapidly, displayed a negative slope conductance of the current-voltage relationships at test potentials > 0 mV, satisfied the envelope of IK-tail test for a single component, and was very sensitive to dofetilide. These characteristics confirm that this current is the rapidly activating component of IK known as IK,r. In addition, dofetilide dramatically prolonged action potential duration in single ventricular myocytes as well as in ventricular myocardium, suggesting that IK,r plays a dominant role in action potential repolarization in fetal mouse heart. From these data we can conclude that fetal mouse cardiac myocytes express IK,r, which functions as a dominant repolarizing K+ current.

Lack of muscarinic regulation of Ca2+ channels in Gi2α gene knockout mouse hearts

2001 ◽  
Vol 280 (5) ◽  
pp. H1989-H1995 ◽  
Author(s):  
Fuhua Chen ◽  
Karsten Spicher ◽  
Meisheng Jiang ◽  
Lutz Birnbaumer ◽  
Glenn T. Wetzel
Keyword(s):  
Knockout Mouse ◽  
Ventricular Myocytes ◽  
Gene Knockout ◽  
Cell Voltage ◽  
Mouse Heart ◽  
Signaling Proteins ◽  
Muscarinic Agonist ◽  
Gene Knockout Mouse ◽  
G Protein Coupled

The purpose of the present study was to examine the role of Gi2α in Ca2+ channel regulation using Gi2α gene knockout mouse ventricular myocytes. The whole cell voltage-clamp technique was used to study the effects of the muscarinic agonist carbachol (CCh) and the β-adrenergic agonist isoproterenol (Iso) on cardiac L-type Ca2+ currents in both 129Sv wild-type (WT) and Gi2α gene knockout (Gi2α−/−) mice. Perfusion with CCh significantly inhibited the Ca2+ current in WT cells, and this effect was reversed by adding atropine to the CCh-containing solution. In contrast, CCh did not affect Ca2+ currents in Gi2α−/− ventricular myocytes. Addition of CCh to Iso-containing solutions attenuated the Iso-stimulated Ca2+ current in WT cardiomyocytes but not in Gi2α−/− cells. These findings demonstrate that, whereas the Iso-Gsα signal pathway is intact in Gi2α gene knockout mouse hearts, these cells lack the inhibitory regulation of Ca2+ channels by CCh. Therefore, Gi2α is necessary for the muscarinic regulation of Ca2+ channels in the mouse heart. Further studies are needed to delineate the possible interaction of Gi and other cell signaling proteins and to clarify the level of interaction of G protein-coupled regulation of L-type Ca2+ current in the heart.

Developmental Changes in β-Adrenergic Modulation of L-Type Ca2+Channels in Embryonic Mouse Heart

1996 ◽  
Vol 78 (3) ◽  
pp. 371-378 ◽  
Author(s):  
R.H. An ◽  
M.P. Davies ◽  
P.A. Doevendans ◽  
S.W. Kubalak ◽  
R. Bangalore ◽  
...  
Keyword(s):  
Developmental Changes ◽  
Mouse Heart ◽  
Embryonic Mouse ◽  
Adrenergic Modulation ◽  
Ca2 Channels

Transgenic upregulation ofIK1in the mouse heart leads to multiple abnormalities of cardiac excitability

2004 ◽  
Vol 287 (6) ◽  
pp. H2790-H2802 ◽  
Author(s):  
Jingdong Li ◽  
Meredith McLerie ◽  
Anatoli N. Lopatin
Keyword(s):  
Action Potential ◽  
Ventricular Myocytes ◽  
Weight Ratio ◽  
Monophasic Action Potential ◽  
Heart Weight ◽  
Slow Phase ◽  
Mouse Heart ◽  
Premature Ventricular Contractions ◽  
Surface Ecg ◽  
Cardiac Excitability

To assess the functional significance of upregulation of the cardiac current ( IK1), we have produced and characterized the first transgenic (TG) mouse model of IK1upregulation. To increase IK1density, a pore-forming subunit of the Kir2.1 (green fluorescent protein-tagged) channel was expressed in the heart under control of the α-myosin heavy chain promoter. Two lines of TG animals were established with a high level of TG expression in all major parts of the heart: line 1 mice were characterized by 14% heart hypertrophy and a normal life span; line 2 mice displayed an increased mortality rate, and in mice ≤1 mo old, heart weight-to-body weight ratio was increased by >100%. In adult ventricular myocytes expressing the Kir2.1-GFP subunit, IK1conductance at the reversal potential was increased ∼9- and ∼10-fold in lines 1 and 2, respectively. Expression of the Kir2.1 transgene in line 2 ventricular myocytes was heterogeneous when assayed by single-cell analysis of GFP fluorescence. Surface ECG recordings in line 2 mice revealed numerous abnormalities of excitability, including slowed heart rate, premature ventricular contractions, atrioventricular block, and atrial fibrillation. Line 1 mice displayed a less severe phenotype. In both TG lines, action potential duration at 90% repolarization and monophasic action potential at 75–90% repolarization were significantly reduced, leading to neuronlike action potentials, and the slow phase of the T wave was abolished, leading to a short Q-T interval. This study provides a new TG model of IK1upregulation, confirms the significant role of IK1in cardiac excitability, and is consistent with adverse effects of IK1upregulation on cardiac electrical activity.

Blockade of Myocardial ATP-sensitive Potassium Channels by Ketamine 

1997 ◽  
Vol 87 (1) ◽  
pp. 68-74 ◽  
Author(s):  
Seong-Hoon Ko ◽  
Sang-Kyi Lee ◽  
Young-Jin Han ◽  
Huhn Choe ◽  
Yong-Geun Kwak ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Katp Channel ◽  
Ventricular Myocytes ◽  
Katp Channels ◽  
Dependent Manner ◽  
Channel Activity ◽  
Concentration Dependent Manner ◽  
Channel Currents ◽  
Inside Out

Background The adenosine triphosphate (ATP)-sensitive potassium (KATP) channel underlies the increase in potassium permeability during hypoxia and ischemia. The increased outward potassium current during ischemia may be an endogenous cardioprotective mechanism. This study was designed to determine the effects of ketamine on KATP channel in rat hearts. Methods Inside-out and cell-attached configurations of patch-clamp techniques and 3 M potassium chloride-filled conventional microelectrodes were used to investigate the effect of ketamine on KATP channel currents in single rat ventricular myocytes and on the action potential duration of rat papillary muscles, respectively. Results Ketamine inhibited KATP channel activity in rat ventricular myocytes in a concentration-dependent manner. In the inside-out patches, the concentration of ketamine for half-maximal inhibition and the Hill coefficient were 62.9 microM and 0.54, respectively. In a concentration-dependent manner, ketamine inhibited pinacidil- and 2,4-dinitrophenol-activated KATP channels in cell-attached patches. The application of ketamine to the intracellular side of membrane patches did not affect the conduction of single-channel currents of KATP channels. Ketamine increased the action potential duration, which was then shortened by pinacidil in a concentration-dependent manner. Conclusions Ketamine inhibited KATP channel activity in a concentration-dependent manner. These results suggest that ketamine may attenuate the cardioprotective effects of the KATP channel during ischemia and reperfusion in the rat myocardium.

TransmembraneI Ca contributes to rate-dependent changes of action potentials in human ventricular myocytes

1999 ◽  
Vol 276 (1) ◽  
pp. H98-H106 ◽  
Author(s):  
Gui-Rong Li ◽  
Baofeng Yang ◽  
Jianlin Feng ◽  
Ralph F. Bosch ◽  
Michel Carrier ◽  
...  
Keyword(s):  
Action Potential ◽  
Ventricular Myocytes ◽  
Slow Component ◽  
Cell Voltage ◽  
High Rate ◽  
Delayed Rectifier ◽  
Rate Dependent ◽  
Ventricular Cells ◽  
The Right

The mechanism of action potential abbreviation caused by increasing rate in human ventricular myocytes is unknown. The present study was designed to determine the potential role of Ca2+ current ( I Ca) in the rate-dependent changes in action potential duration (APD) in human ventricular cells. Myocytes isolated from the right ventricle of explanted human hearts were studied at 36°C with whole cell voltage and current-clamp techniques. APD at 90% repolarization decreased by 36 ± 4% when frequency increased from 0.5 to 2 Hz. Equimolar substitution of Mg2+ for Ca2+ significantly decreased rate-dependent changes in APD (to 6 ± 3%, P < 0.01). Peak I Ca was decreased by 34 ± 3% from 0.5 to 2 Hz ( P < 0.01), and I Ca had recovery time constants of 65 ± 12 and 683 ± 39 ms at −80 mV. Action potential clamp demonstrated a decreasing contribution of I Ca during the action potential as rate increased. The rate-dependent slow component of the delayed rectifier K+current ( I Ks) was not observed in four cells with an increase in frequency from 0.5 to 3.3 Hz, perhaps because the I Ks is so small that the increase at a high rate could not be seen. These results suggest that reduction of Ca2+influx during the action potential accounts for most of the rate-dependent abbreviation of human ventricular APD.

Abnormalities of K+ and Ca2+ currents in ventricular myocytes from rats with chronic diabetes

1995 ◽  
Vol 269 (4) ◽  
pp. H1288-H1296 ◽  
Author(s):  
D. W. Wang ◽  
T. Kiyosue ◽  
S. Shigematsu ◽  
M. Arita
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Ventricular Myocytes ◽  
Slow Component ◽  
Outward Current ◽  
Cell Voltage ◽  
Transient Outward Current ◽  
Inactivation Curve ◽  
Ionic Mechanisms ◽  
In Cells

Ionic mechanisms related to the prolongation of cardiac action potential in rats with chronic diabetes mellitus were studied using whole cell voltage-clamp techniques. Diabetes was induced by injection of streptozotocin (STZ; 65 mg/kg body wt) into the tail vein, and ventricular myocytes were isolated from STZ-injected rats (24-30 wk) and from age-matched normal rats. The current densities of transient outward current (Ito), a steady-state outward current, and L-type Ca2+ current (ICa) were significantly smaller in cells from diabetic animals. In addition, the kinetics of Ito of diabetic cells were modified. 1) The decay of Ito was well fitted by a sum of two exponential components in normal cells; there was only one (slow) component in the diabetic cells. 2) The steady-state inactivation curve of Ito in diabetic cells shifted by 5 mV in the negative direction. 3) Recovery from inactivation of Ito was slower in cells from diabetic animals. These alterations in Ito and the steady-state outward current can account for most of the action potential prolongation heretofore documented. The decrease of ICa may possibly be related to the depressed contraction seen in chronic diabetic mellitus.

Stage-dependent changes in membrane currents in rats with monocrotaline-induced right ventricular hypertrophy

1997 ◽  
Vol 272 (6) ◽  
pp. H2833-H2842 ◽  
Author(s):  
J. K. Lee ◽  
I. Kodama ◽  
H. Honjo ◽  
T. Anno ◽  
K. Kamiya ◽  
...  
Keyword(s):  
Action Potential ◽  
Ventricular Hypertrophy ◽  
Ventricular Myocytes ◽  
Early Stage ◽  
Weight Ratio ◽  
Outward Current ◽  
Transient Outward Current ◽  
Significant Difference ◽  
And Control ◽  
Action Potential Configuration

Sequential changes in action potential configuration, 4-amino-pyridine-sensitive transient outward current (Ito), and L-type calcium current (ICa) in association with hypertrophy were investigated in ventricular myocytes from rats with monocrotaline (MCT)-induced pulmonary hypertension. The tissue weight ratio of right ventricle (RV) to left ventricle plus septum 14 and 28 days after a subcutaneous injection of MCT increased by 29.7 and 77.2%, respectively. Action potential duration (APD) of RV cells from MCT rats increased progressively, prolonged by 73.2 and 92.2% on days 14 and 28, respectively. The current density of Ito in RV cells from MCT rats on day 14 (32.5 +/- 4.5 pA/pF, n = 13) was significantly larger than in controls (26.8 +/- 4.5 pA/pF, n = 8; P < 0.05). On day 28, however, Ito density in MCT rats (15.3 +/- 4.6 pA/pF, n = 9) was significantly less than in controls (27.3 +/- 4.2 pA/pF, n = 10; P < 0.05). There were no differences in the voltage dependence of steady-state activation and inactivation of Ito between MCT and control rats. ICa density in MCT rats on day 14 (15.7 +/- 2.6 pA/pF, n = 10) was significantly larger than in controls (10.0 +/- 2.3 pA/pF, n = 10; P < 0.05), but there was no significant difference in Ito density between MCT rats (8.3 +/- 3.7 pA/pF, n = 10) and controls (11.6 +/- 3.0 pA/pF, n = 10) on day 28. These findings suggest that hypertrophy of mammalian hearts may cause stage-dependent changes in Ito and ICa density of ventricular myocytes. The APD prolongation in the early stage of hypertrophy may be caused mainly by an increase in ICa density, whereas the APD prolongation in the late stage may be ascribed to a reduction in Ito density.

scholarly journals Zinc Enhances the Inhibitory Effects of Strychnine-Sensitive Glycine Receptors in Mouse Hippocampal Neurons

2007 ◽  
Vol 98 (6) ◽  
pp. 3666-3676 ◽  
Author(s):  
Hai Xia Zhang ◽  
Liu Lin Thio
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Hippocampal Slices ◽  
Glycine Receptors ◽  
Inhibitory Effects ◽  
Action Potential Firing ◽  
Embryonic Mouse ◽  
Potential Firing

Although extracellular Zn2+ is an endogenous biphasic modulator of strychnine-sensitive glycine receptors (GlyRs), the physiological significance of this modulation remains poorly understood. Zn2+ modulation of GlyR may be especially important in the hippocampus where presynaptic Zn2+ is abundant. Using cultured embryonic mouse hippocampal neurons, we examined whether 1 μM Zn2+, a potentiating concentration, enhances the inhibitory effects of GlyRs activated by sustained glycine applications. Sustained 20 μM glycine (EC25) applications alone did not decrease the number of action potentials evoked by depolarizing steps, but they did in 1 μM Zn2+. At least part of this effect resulted from Zn2+ enhancing the GlyR-induced decrease in input resistance. Sustained 20 μM glycine applications alone did not alter neuronal bursting, a form of hyperexcitability induced by omitting extracellular Mg2+. However, sustained 20 μM glycine applications depressed neuronal bursting in 1 μM Zn2+. Zn2+ did not enhance the inhibitory effects of sustained 60 μM glycine (EC70) applications in these paradigms. These results suggest that tonic GlyR activation could decrease neuronal excitability. To test this possibility, we examined the effect of the GlyR antagonist strychnine and the Zn2+ chelator tricine on action potential firing by CA1 pyramidal neurons in mouse hippocampal slices. Co-applying strychnine and tricine slightly but significantly increased the number of action potentials fired during a depolarizing current step and decreased the rheobase for action potential firing. Thus Zn2+ may modulate neuronal excitability normally and in pathological conditions such as seizures by potentiating GlyRs tonically activated by low agonist concentrations.

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