Bradykinin induced a positive chronotropic effect via stimulation of T- and L-type calcium currents in heart cells

2003 ◽  
Vol 81 (3) ◽  
pp. 247-258 ◽  
Author(s):  
Nesrine El-Bizri ◽  
Ghassan Bkaily ◽  
Shimin Wang ◽  
Danielle Jacques ◽  
Domenico Regoli ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Ionic Current ◽  
Calcium Currents ◽  
Heart Cells ◽  
Dependent Manner ◽  
Chronotropic Effect ◽  
Chick Heart ◽  
Chronotropic Effects ◽  
Positive Chronotropic Effect ◽  
Stimulation Of

Using Fluo-3 calcium dye confocal microscopy and spontaneously contracting embryonic chick heart cells, bradykinin (10–10 M) was found to induce positive chronotropic effects by increasing the frequency of the transient increase of cytosolic and nuclear free Ca2+. Pretreatment of the cells with either B1 or B2 receptor antagonists (R126 and R817, respectively) completely prevented bradykinin (BK) induced positive chronotropic effects on spontaneously contracting single heart cells. Using the whole-cell voltage clamp technique and ionic substitution to separate the different ionic current species, our results showed that BK (10–6 M) had no effect on fast Na+ inward current and delayed outward potassium current. However, both L- and T-type Ca2+ currents were found to be increased by BK in a dose-dependent manner (10–10–10–7 M). The effects of BK on T- and L-type Ca2+ currents were partially blocked by the B1 receptor antagonist [Leu8]des-Arg9-BK (R592) (10–7 M) and completely reversed by the B2 receptor antagonist D-Arg[Hyp3,D-Phe7,Leu8]BK (R-588) (10–7 M) or pretreatment with pertussis toxin (PTX). These results demonstrate that BK induced a positive chronotropic effect via stimulation of T- and L-type Ca2+ currents in heart cells mainly via stimulation of B2 receptor coupled to PTX-sensitive G-proteins. The increase of both types of Ca2+ current by BK in heart cells may explain the positive inotropic and chronotropic effects of this hormone.Key words: chick heart cells, bradykinin, B1 receptor, B2 receptor, Ca2+, Na+, K+ currents.

Effects of WAY100635, a selective 5-HT1A-receptor antagonist on the micturition-reflex pathway in the rat

2001 ◽  
Vol 280 (5) ◽  
pp. R1407-R1413 ◽  
Author(s):  
Hidehiro Kakizaki ◽  
Mitsuharu Yoshiyama ◽  
Tomohiko Koyanagi ◽  
William C. De Groat
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Receptor Antagonist ◽  
Intrathecal Injection ◽  
Cervical Cord ◽  
Dependent Manner ◽  
Reflex Pathway ◽  
Micturition Reflex ◽  
Female Wistar Rats ◽  
Stimulation Of

5-Hydroxytryptamine (5-HT) receptors in the central nervous system have been implicated in the control of micturition. The present study was undertaken to evaluate the effects of a selective 5-HT1A-receptor antagonist { N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY100635)} on the micturition-reflex pathway in urethane-anesthetized female Wistar rats. Rhythmic isovolumetric bladder contractions evoked by bladder distension were abolished by 0.3- to 3-mg/kg iv or 30- to 100-μg intrathecal (it) administration of WAY100635 in a dose-dependent manner for periods of 3–15 min. Intrathecal injection of WAY100635 was effective only if injected at the L6-S1 spinal cord level, but not at the thoracic or cervical cord levels. WAY100635 (30–100 μg it) significantly reduced the amplitude of bladder contractions evoked by electrical stimulation of the pontine micturition center. However, the field potentials in the rostral pons evoked by electrical stimulation of pelvic nerve were not affected by intrathecal or intravenous injection of WAY100635. These results suggest that 5-HT1A receptors at the L6-S1 level of the spinal cord have an important role in the tonic control of the descending limb of the micturition-reflex pathway in the rat.

Field Stimulation of Isolated Chick Heart Cells.

1999 ◽  
Vol 10 (1) ◽  
pp. 92-107 ◽  
Author(s):  
BRADLEY A. STONE ◽  
MELVYN LIEBERMAN ◽  
WANDA KRASSOWSKA
Keyword(s):  
Heart Cells ◽  
Field Stimulation ◽  
Chick Heart ◽  
Stimulation Of

Effects of endothelin on spontaneous contractions in lymph vessels

1999 ◽  
Vol 277 (2) ◽  
pp. H459-H466 ◽  
Author(s):  
Hiroshi Sakai ◽  
Fumitaka Ikomi ◽  
Toshio Ohhashi
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscles ◽  
Significant Inhibition ◽  
Lymphatic Endothelial Cells ◽  
Chronotropic Effect ◽  
Inotropic Effects ◽  
Mechanical Removal ◽  
Spontaneous Contractions ◽  
Positive Chronotropic Effect ◽  
Stimulation Of

A mode of action of endothelin (ET) on spontaneous contractions was investigated in ring preparations of isolated bovine mesenteric lymphatics. ET-1 at concentrations between 10−10 and 10−9 M caused a dose-dependent increase in the frequency of spontaneous contractions. The specific ETA-receptor antagonist BQ-123 (5 × 10−7 M) caused a significant inhibition of the ET-1-induced positive chronotropic effect in the ring preparations with and without the endothelium. Mechanical denudation of the lymphatic endothelial cells produced a significant potentiation of the ET-induced positive chronotropic effect. BQ-3020 (10−8–10−7M), a selective ETB-receptor agonist, induced dose dependently negative chronotropic and inotropic effects on the spontaneous contractions in the ring preparations with intact endothelium. Mechanical removal of the endothelium caused a significant reduction of the BQ-3020-induced negative chronotropic and inotropic effects. The ET-1-induced positive chronotropic effect was potentiated by pretreatment with N ω-nitro-l-arginine methyl ester (l-NAME) (10−5 M) but unaffected by aspirin (10−5 M). Additional treatment with l-arginine (10−4 M) completely reversed the l-NAME-mediated potentiation of the ET-induced chronotropic effect. These results suggest that stimulation of ETA receptors on the lymphatic smooth muscles causes a positive chronotropic effect on the spontaneous contractions, and stimulation of ETB receptors on the lymphatic endothelial cells induces a release of nitric oxide, which results in the chronotropic and inotropic effects on spontaneous contractions in isolated bovine mesenteric lymphatics.

scholarly journals Metabolic and functional consequences of cytosolic 5′-nucleotidase-IA overexpression in neonatal rat cardiomyocytes

2003 ◽  
Vol 285 (3) ◽  
pp. H991-H998 ◽  
Author(s):  
Graciela B. Sala-Newby ◽  
Nicola V. E. Freeman ◽  
Maria A. Curto ◽  
Andrew C. Newby
Keyword(s):  
Neonatal Rat ◽  
Nucleoside Transporter ◽  
Chronotropic Effect ◽  
Rat Cardiomyocytes ◽  
Adenosine Receptor Antagonist ◽  
Neonatal Rat Cardiomyocytes ◽  
Functional Consequences ◽  
Chronotropic Effects ◽  
Simulated Hypoxia ◽  
Positive Chronotropic Effect

Adenosine exerts a spectrum of energy-preserving actions on the heart negative chronotropic effects. The pathways leading to adenosine formation have remained controversial. In particular, although cytosolic 5′-nucleotidases can catalyze adenosine formation in cardiomyocytes, their contribution to the actions of adenosine has not been documented previously. We recently cloned two closely related AMP-preferring cytosolic 5′-nucleotidases (cN-IA and -IB); the A form predominates in the heart. In this study, we overexpressed pigeon cN-IA in neonatal rat cardiomyocytes using an adenovirus. cN-IA overexpression increased adenosine formation and release into the medium caused by simulated hypoxia and by isoproterenol in the absence and presence of inhibitors of adenosine metabolism. Adenosine release was not affected by an ecto-5′-nucleotidase inhibitor, α,β-methylene-ADP, but was affected by a nucleoside transporter, dipyridamole. The positive chronotropic effect of isoproterenol (130 ±3 vs. 100 ±4 beats/min) was inhibited (107 ±3 vs. 94 ±3 beats/min) in cells overexpressing cN-IA, and this was reversed by the addition of the adenosine receptor antagonist 8-( p-sulfophenyl)theophilline (120 ± 3 vs. 90 ± 4 beats/min). Our results demonstrate that overexpressed cN-IA can be sufficiently active in cardiomyocytes to generate physiologically effective concentrations of adenosine at its receptors.

scholarly journals Pertussis toxin does not inhibit muscarinic-receptor-mediated phosphoinositide hydrolysis or calcium mobilization

1985 ◽  
Vol 227 (3) ◽  
pp. 933-937 ◽  
Author(s):  
S B Masters ◽  
M W Martin ◽  
T K Harden ◽  
J H Brown
Keyword(s):  
Muscarinic Receptor ◽  
Muscarinic Receptors ◽  
Pertussis Toxin ◽  
Inositol Phosphate ◽  
Regulatory Protein ◽  
Calcium Mobilization ◽  
Phosphoinositide Hydrolysis ◽  
Heart Cells ◽  
Chick Heart ◽  
Stimulation Of

Pertussis toxin was used to examine the role of the inhibitory guanine nucleotide regulatory protein, Ni, in muscarinic-receptor-mediated stimulation of phosphoinositide turnover and calcium mobilization. In cultured chick heart cells, pertussis-toxin treatment inhibited muscarinic-receptor-mediated attenuation of isoprenaline-stimulated cyclic AMP accumulation. This finding is consistent with the proposal that pertussis toxin blocks the capacity of Ni to couple muscarinic receptors to adenylate cyclase. In contrast, treatment of chick heart cells or 1321N1 human astrocytoma cells with pertussis toxin did not block muscarinic-receptor-mediated stimulation of phosphoinositide hydrolysis, as measured by [3H]inositol phosphate accumulation in the presence of Li+. Pertussis-toxin treatment also had little effect on basal and muscarinic-receptor-stimulated phosphatidylinositol synthesis, as measured by the incorporation of [3H]inositol into phosphatidylinositol. Activation of muscarinic receptors also enhances the rate of unidirectional 45Ca2+ efflux in 1321N1 cells; this response, like phosphoinositide hydrolysis, was not prevented by pertussis-toxin treatment. Our data suggest that muscarinic receptors are not coupled to phosphoinositide hydrolysis or calcium mobilization through Ni.

Overdrive suppression of automaticity in cultured chick myocardial cells

1980 ◽  
Vol 238 (1) ◽  
pp. H24-H30 ◽  
Author(s):  
A. Pelleg ◽  
S. Vogel ◽  
L. Belardinelli ◽  
N. Sperelakis
Keyword(s):  
Heart Cells ◽  
Spontaneous Firing ◽  
Embryonic Chick ◽  
Quiescent Cells ◽  
Chick Heart ◽  
Embryonic Chick Heart ◽  
Overdrive Suppression ◽  
Time Courses ◽  
Spontaneous Firing Rate ◽  
Stimulation Of

Overdrive suppression in automatic cells and postdrive hyperpolarization in quiescent cells were examined in cultured embryonic chick heart cells. Cells were enzymatically separated from 3-day-old whole hearts and from 16-day-old atria and ventricles. The dispersed cells were allowed to reaggregate into small spheres (aneural) and maintained in culture for 1--4 wk. Quiescent reaggregates (all ventricular reaggregates and some of the atrial) demonstrated postdrive transient hyperpolarization of up to 5 mV. The spontaneously beating reaggregates (some of the atrial and all of the 3-day-old hearts) demonstrated overdrive suppression of automaticity. The faster the predrive spontaneous firing rate, the shorter was the overdrive suppression period. Prolongation of the drive period increased the duration of the overdrive suppression. The time courses of recovery from both overdrive suppression and postdrive hyperpolarization were similar. Atropine (10(-5) M) did not affect the phenomena. Ouabain (10(-6) M) reduced the postdrive hyperpolarization and shortened the duration of overdrive suppression. It was concluded that overdrive suppression and postdrive hyperpolarization a) occur in cultured chick ventricular and atrail cells; b) occur in early embryonic stages of development; c) occur independently of cholinergic receptors; d) are dependent on stimulation of an elecrogenic Na-K pump.

Effects of calcium channel blockers on spontaneous electrical activity of freshly isolated three-day-old embryonic chick ventricle

1996 ◽  
Vol 8 (5) ◽  
pp. 921 ◽  
Author(s):  
P Prakash ◽  
P Meera ◽  
O Tripathi
Keyword(s):  
Na Channel ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Embryonic Chick ◽  
Na Channels ◽  
Chronotropic Effect ◽  
High Doses ◽  
Dose Dependent ◽  
Ca2 Channels ◽  
Positive Chronotropic Effect

The effects of four major types of organic Ca2+ channel blockers, verapamil, nifedipine, diltiazem and fendiline and of tetrodotoxin (TXX), a fast Na+ channel blocker, on the action potential (AP) of freshly isolated 3-day-old embryonic chick ventricle (3d ECV) were investigated to resolve the controversy about the ionic basis of upstroke. The APs were characterized by a maximum diastolic potential (MDP) of -60 mV, an overshoot (Eov) of 16 mV and a maximum upstroke velocity (+Vmax) of 42 V s-1. All four Ca2+ channel blockers (0.1-40 microM) and TTX (0.1-80 nM) produced a dose-dependent reduction in +Vmax and Eov. MDP was also reduced by Ca2+ channel blockers in a dose-dependent manner but was unaffected by TTX. A significant linear correlation between MDP and +Vmax was observed for verapamil (r = 0.99), nifedipine (r = 0.99), diltiazem (r = 0.96) and fendiline (r = 0.98). Surprisingly, all Ca2+ channel blockers produced a dose-dependent positive chronotropic effect leading to cessation of firing at high doses (20-40 microM). In preparations becoming quiescent with high doses of verapamil (20-40 microM), elevated extracellular concentrations of Ca2+ (up to 9.6 nM) and isoproterenol (0.5-40 microM) failed to restore spontaneous APs. Electrical stimulation also failed to elicit APs in preparations inhibited by verapamil, diltiazem and fendiline. The inhibition of +Vmax by TTX demonstrates that fast Na+ channels were involved in the upstroke of AP in 3d ECV. Voltage-dependent inactivation of fast Na+ channels during depolarization (reduction in MDP) by the Ca2+ channel blockers explains their inhibitory effect on +Vmax and indicates that L-type Ca2+ channels had no significant role in the upstroke. A positive chronotropic effect of the Ca2+ channel blockers further suggests that slow Ca2+ channels are not involved in automaticity in freshly isolated 3d ECV.

Bethanidine increased Na+ and Ca2+ currents and caused a positive inotropic effect in heart cells

1988 ◽  
Vol 66 (2) ◽  
pp. 190-196 ◽  
Author(s):  
G. Bkaily ◽  
M. D. Payet ◽  
M. Benabderrazik ◽  
J.-F. Renaud ◽  
R. Sauvé ◽  
...  
Keyword(s):  
Positive Inotropic Effect ◽  
Inhibitory Effect ◽  
Inotropic Effect ◽  
Heart Cells ◽  
Dependent Manner ◽  
Isolated Atria ◽  
Cell Current ◽  
Chick Heart ◽  
Embryonic Chick Heart ◽  
Dose Dependent

The effects of bethanidine sulphate, a pharmacological analog of the cardiac antibrillatory drug, bretylium tosylate, were studied on action potentials (APs) and K+, Na+, and Ca2+ currents of single cultured embryonic chick heart cells using the whole-cell current clamp and voltage clamp technique. Extracellular application of bethanidine (3 × 10−4 M) increased the overshoot and the duration of the APs and greatly decreased the outward K+ current (IK) and potentiated the inward fast Na+ currents (INa) and the inward slow calcium current (ICa). However, intracellular introduction of bethanidine (10−4 M) blocked INa. In isolated atria of rat, bethanidine increased the force of contraction in a dose-dependent manner. These findings suggest that when applied extracellularly, bethanidine exerts a potentiating effect on the myocardial fast Na+ current and slow Ca2+ current and an inhibitory effect of IK. The positive inotropic effect of bethanidine could be due, at least in part, to an increase of Ca2+ influx via the slow Ca2+ channel and the Na–Ca exchange. It is suggested that the decrease of IK by bethanidine may account for its antifibrillatory action.

Chronotropic function in spontaneously diabetic BB rats

1989 ◽  
Vol 67 (5) ◽  
pp. 519-521 ◽  
Author(s):  
Sasanka Ramanadham ◽  
Gail M. McGrath ◽  
John H. McNeill
Keyword(s):  
Direct Consequence ◽  
Wistar Rat ◽  
Diabetic Rats ◽  
Chronotropic Effect ◽  
Chronotropic Response ◽  
Bb Rats ◽  
Streptozotocin Diabetic Rats ◽  
Chronotropic Effects ◽  
Altered Thyroid ◽  
Positive Chronotropic Effect

In the present study, isolated atrial function in spontaneously diabetic BB Wistar rats maintained for 12 weeks on a low (BB-LI) and a high (BB-HI) dosage of insulin was examined. Basal atrial rates were unchanged in the diabetic animals, relative to nondiabetic littermates (ND-BB) or Wistar controls. The BB-HI animals were euglycemic and responded to isoproterenol in a similar manner to the ND-BB and Wistar control animals. In contrast, BB-LI animals remained hyperglycemic and exhibited lower responses to the maximum chronotropic effects of isoproterenol. Plasma thyroid hormone levels were unaltered in the BB-diabetic animals. These results therefore reveal an absence of bradycardia and hypothyroidism in spontaneously diabetic BB rats, in contrast to previous observations in streptozotocin diabetic rats. However, a decrease in chronotropic response to isoproterenol was still noted in the BB-LI animals. These findings suggest that decreased positive chronotropic effect of isoproterenol in diabetes may not be a direct consequence of altered thyroid status.Key words: BB Wistar rat, diabetes, chronotropic response, β-receptors.

Sign in / Sign up

Export Citation Format

Share Document