Involvement of Na+/Ca2+ exchanger in catecholamine-induced increase in intracellular calcium in cardiomyocytes

2006 ◽  
Vol 290 (1) ◽  
pp. H373-H380 ◽  
Author(s):  
Harjot K. Saini ◽  
Onkar N. Tripathi ◽  
Shetuan Zhang ◽  
Vijayan Elimban ◽  
Naranjan S. Dhalla
Keyword(s):  
Purinergic Receptor ◽  
Cyclopiazonic Acid ◽  
Channel Blockers ◽  
Inhibitory Effects ◽  
Inotropic Action ◽  
Rat Cardiomyocytes ◽  
Isolated Hearts ◽  
Adrenoceptor Agonist ◽  
Significant Depression ◽  
Intracellular Ca

Although sarcolemmal (SL) Na+/Ca2+ exchanger is known to regulate the intracellular Ca2+ concentration ([Ca2+]i), its involvement in catecholamine-induced increase in [Ca2+]i is not fully understood. To gain some information in this regard, isolated rat cardiomyocytes were treated with different agents, which are known to modify Ca2+ movements, in the absence or presence of a β-adrenoceptor agonist, isoproterenol, and [Ca2+]i in cardiomyocytes was determined spectrofluorometrically with fura-2 AM. Treatment with isoproterenol did not alter [Ca2+]i in quiescent cardiomyocytes, whereas the ATP (purinergic receptor agonist)-induced increase in [Ca2+]i was significantly potentiated by isoproterenol. Unlike ryanodine and cyclopiazonic acid, which affect the sarcoplasmic reticulum function, SL L-type Ca2+ channel blockers verapamil and diltiazem, as well as a SL Ca2+-pump inhibitor, vanadate, caused a significant depression in the isoproterenol-induced increase in [Ca2+]i. The SL Na+/Ca2+ exchange blockers amiloride, Ni2+, and KB-R7943 also attenuated the isoproterenol-mediated increase in [Ca2+]i. Combination of KB-R7943 and verapamil showed additive inhibitory effects on the isoproterenol-induced increase in [Ca2+]i. The isoproterenol-induced increase in [Ca2+]i in KCl-depolarized cardiomyocytes was augmented by low Na+; this augmentation was significantly depressed by treatment with KB-R7943. The positive inotropic action of isoproterenol in isolated hearts was also reduced by KB-R7943. These data suggest that in addition to SL L-type Ca2+ channels, SL Na+/Ca2+ exchanger seems to play an important role in catecholamine-induced increase in [Ca2+]i in cardiomyocytes.

Mechanical strain-induced Ca2+waves are propagated via ATP release and purinergic receptor activation

2000 ◽  
Vol 279 (2) ◽  
pp. C295-C307 ◽  
Author(s):  
H. Sauer ◽  
J. Hescheler ◽  
M. Wartenberg
Keyword(s):  
Gap Junctions ◽  
Purinergic Receptor ◽  
Mechanical Strain ◽  
Atp Release ◽  
Anion Channel ◽  
Receptor Activation ◽  
Disulfonic Acid ◽  
Channel Blockers ◽  
Junctional Coupling ◽  
Intracellular Ca

Mechanical strain applied to prostate cancer cells induced an intracellular Ca2+ (Cai 2+) wave spreading with a velocity of 15 μm/s. Cai 2+ waves were not dependent on extracellular Ca2+ and membrane potential because propagation was unaffected in high-K+ and Ca2+-free solution. Waves did not depend on the cytoskeleton or gap junctions because cytochalasin B and nocodazole, which disrupt microfilaments and microtubules, respectively, and 1-heptanol, which uncouples gap junctions, were without effects. Fluorescence recovery after photobleaching experiments revealed an absence of gap junctional coupling. Cai 2+ waves were inhibited by the purinergic receptor antagonists basilen blue and suramin; by pretreatment with ATP, UTP, ADP, UDP, 2-methylthio-ATP, and benzoylbenzoyl-ATP; after depletion of ATP by 2-deoxyglucose; and after ATP scavenging by apyrase. Waves were abolished by the anion channel inhibitors 5-nitro-2-(3-phenylpropylamino)benzoic acid, tamoxifen, 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid, niflumic acid, and gadolinium. ATP release following strain was significantly inhibited by anion channel blockers. Hence, ATP is secreted via mechanosensitive anion channels and activates purinergic receptors on the same cell or neighboring cells in an autocrine and paracrine manner, thus leading to Cai 2+ wave propagation.

scholarly journals Roles of extracellular ions and pH in 5-HT-induced sperm motility in marine bivalve

Reproduction ◽  
2014 ◽  
Vol 147 (3) ◽  
pp. 331-345 ◽  
Author(s):  
Sayyed Mohammad Hadi Alavi ◽  
Natsuki Matsumura ◽  
Kogiku Shiba ◽  
Naoki Itoh ◽  
Keisuke G Takahashi ◽  
...  
Keyword(s):  
Sperm Motility ◽  
Pacific Oyster ◽  
Manila Clam ◽  
Marine Bivalve ◽  
Channel Blockers ◽  
Inhibitory Effects ◽  
Patinopecten Yessoensis ◽  
Independent Mechanism ◽  
Intracellular Ca ◽  
Extracellular Ions

Factors that inhibit and stimulate the initiation of sperm motility were determined for Manila clam (Ruditapesphilippinarum), Pacific oyster (Crassostrea gigas), and Japanese scallop (Patinopecten yessoensis). Compared with artificial seawater (ASW), serotonin (5-hydroxytryptamine creatinine sulfate, 5-HT) could fully trigger sperm motility and increase sperm velocity and motility duration. Sperm motility was decreased in ASW at pH 6.5–7.0 and suppressed at pH 4.0. In Manila clam and Pacific oyster, 5-HT could overcome the inhibitory effects of acidic pH on sperm motility. In the presence of nigericin (a K+/H+exchanger), sperm motility was only triggered at pH 8.3. Testicular fluid K+concentrations were two- to fourfold higher than that in ASW. Sperm motility and velocity were decreased in ASW or 5-HT containing ≥40 mM K+or ≥2.5 mM 4-aminopyridine, suggesting K+efflux requirement to initiate motility. Sperm motility and velocity were reduced in ASW or 5-HT containing EGTA or W-7, suggesting that extracellular Ca2+is required for Ca2+/calmodulin-dependent flagellar beating. Ca2+influx occurs via Ca2+channels because sperm motility and velocity were decreased in both ASW and 5-HT containing T-type and L-type Ca2+channel blockers. 5-HT-dependent initiation of sperm motility was associated with intracellular Ca2+rise, which was comparable to that seen in ASW but was not observed in the presence of EGTA or a Ca2+channel blocker. Extracellular Na+is also essential for sperm motility initiation via regulation of Na+/Ca2+exchange. Overall, 5-HT-dependent initiation of sperm motility in marine bivalve mollusks is an osmolality-independent mechanism and regulated by extracellular pH, K+, Ca2+, and Na+.

Contribution of Ca2+-Permeable AMPA/KA Receptors to Glutamate-Induced Ca2+ Rise in Embryonic Lumbar Motoneurons In Situ

2000 ◽  
Vol 83 (1) ◽  
pp. 50-59 ◽  
Author(s):  
Friedrich Metzger ◽  
Anna Kulik ◽  
Michael Sendtner ◽  
Klaus Ballanyi
Keyword(s):  
Ampa Receptors ◽  
Cyclopiazonic Acid ◽  
Channel Blockers ◽  
Voltage Gated ◽  
Fura 2 ◽  
Combined Application ◽  
Predominant Component ◽  
Intracellular Ca ◽  
Trophic Signaling

Intracellular Ca2+([Ca2+]i) was fluorometrically measured with fura-2 in lumbar motoneurons of acutely isolated spinal cord slices from embryonic rats. In ester-loaded cells, bath-applied glutamate (3 μM to 1 mM) evoked a [Ca2+]i increase by up to 250 nM that was abolished by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) plus 2-amino-5-phosphonovalerate (APV). CNQX or APV alone reduced the response by 82 and 25%, respectively. The glutamatergic agonists kainate (KA), quisqualate (QUI), and S-α-amino-3-hydroxy-5-methyl-4-isoxalone (S-AMPA) evoked a similar [Ca2+]i transient as glutamate. N-methyl-d-aspartate (NMDA) was only effective to increase [Ca2+]i in Mg2+-free saline, whereas [1S,3R]-1-aminocyclopentane-1,3-dicarboxylic acid ([1S,3R]-ACPD) had no effect. The glutamate-induced [Ca2+]i rise was suppressed in Ca2+-free superfusate. Depletion of Ca2+ stores with cyclopiazonic acid (CPA) did not affect the response. Thirty-six percent of the [Ca2+]i increase in response to membrane depolarization induced by a 50 mM K+ solution persisted on combined application of the voltage-gated Ca2+channel blockers nifedipine, ω-conotoxin-GVIA and ω-agatoxin-IVA. In fura-2 dialyzed motoneurons, the glutamate-induced [Ca2+]i increase was attenuated by ∼70% after changing from current to voltage clamp. Forty percent of the remaining [Ca2+]i transient and 20% of the concomitant inward current of 0.3 nA were blocked by Joro spider toxin-3 (JSTX). The results show that voltage-gated Ca2+channels, including a major portion of R-type channels, constitute the predominant component of glutamate-induced [Ca2+]i rises. NMDA and Ca2+-permeable KA/AMPA receptors contribute about equally to the remaining component of the Ca2+ rise. The results substantiate previous assumptions that Ca2+ influx through JSTX-sensitive KA/AMPA receptors is involved in (trophic) signaling in developing motoneurons.

Temporal and spatial dynamics underlying capacitative calcium entry in human colonic smooth muscle

2008 ◽  
Vol 294 (1) ◽  
pp. G88-G98 ◽  
Author(s):  
Jason R. Kovac ◽  
Tom Chrones ◽  
Stephen M. Sims
Keyword(s):  
Smooth Muscle ◽  
High Speed ◽  
Imaging Techniques ◽  
Spatial Dynamics ◽  
Cyclopiazonic Acid ◽  
Smooth Muscle Contraction ◽  
Bathing Solution ◽  
Channel Blockers ◽  
Intracellular Ca ◽  
Inward Currents

Following smooth muscle excitation and contraction, depletion of intracellular Ca2+ stores activates capacitative Ca2+ entry (CCE) to replenish stores and sustain cytoplasmic Ca2+ (Ca2+i) elevations. The objectives of the present study were to characterize CCE and the Ca2+i dynamics underlying human colonic smooth muscle contraction by using tension recordings, fluorescent Ca2+-indicator dyes, and patch-clamp electrophysiology. The neurotransmitter acetylcholine (ACh) contracted tissue strips and, in freshly isolated colonic smooth muscle cells (SMCs), caused elevation of Ca2+i as well as activation of nonselective cation currents. To deplete Ca2+i stores, the sarcoplasmic reticulum Ca2+-ATPase (SERCA) inhibitors thapsigargin and cyclopiazonic acid were added to a Ca2+-free bathing solution. Under these conditions, addition of extracellular Ca2+ (3 mM) elicited increased tension that was inhibited by the cation channel blockers SKF-96365 (10 μM) and lanthanum (100 μM), suggestive of CCE. In a separate series of experiments on isolated SMCs, SERCA inhibition generated a gradual and sustained inward current. When combined with high-speed Ca2+-imaging techniques, the CCE-evoked rise of Ca2+i was associated with inward currents carrying Ca2+ that were inhibited by SKF-96365. Regional specializations in Ca2+ influx and handling during CCE were observed. Distinct “hotspot” regions of Ca2+ rise and plateau were evident in 70% of cells, a feature not previously recognized in smooth muscle. We propose that store-operated Ca2+ entry occurs in hotspots contributing to localized Ca2+ elevations in human colonic smooth muscle.

scholarly journals Inhibitory effects of calcium channel blockers on thyroid hormone uptake in neonatal rat cardiomyocytes

2001 ◽  
Vol 281 (5) ◽  
pp. H1985-H1991 ◽  
Author(s):  
Frank A. Verhoeven ◽  
Ellis P. C. M. Moerings ◽  
Jos M. J. Lamers ◽  
Georg Hennemann ◽  
Theo J. Visser ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Inhibitory Effect ◽  
Neonatal Rat ◽  
Channel Blockers ◽  
Inhibitory Effects ◽  
Rat Cardiomyocytes ◽  
Old Rats ◽  
Relative Decline ◽  
Dose Dependent ◽  
Dose Dependent Effect

The effects of the Ca2+ channel blockers verapamil, nifedipine, and diltiazem on triiodothyronine (T3) and thyroxine (T4) uptake were tested in cultured cardiomyocytes from 2-day-old rats. Experiments were performed at 37°C in medium with 0.5% BSA for [125I]T3 (100 pM) or 0.1% BSA for [125I]T4 (350 pM). The 15-min uptake of [125I]T3 was 0.124 ± 0.013 fmol/pM free T3 ( n = 6); [125I]T4 uptake was 0.032 ± 0.003 fmol/pM free T4 ( n = 12). Neither T3 nor T4 uptake was affected by 1% DMSO (diluent for nifedipine and verapamil). Uptake of [125I]T3 but not of [125I]T4 was dose dependently reduced by incubation with 1–100 μM verapamil (49–87%, P < 0.05) or nifedipine (53–81%, P < 0.05). The relative decline in [125I]T3 uptake after 4 h of incubation with 10 μM verapamil or nifedipine was less than after 15 min or 1 h, indicating that the major inhibitory effect of the Ca2+ channel blockers occurred at the level of the plasma membrane. The reduction of nuclear [125I]T3binding by 10 μM verapamil or nifedipine was proportional to the reduction of cellular [125I]T3 uptake. Diltiazem (1–100 μM) had no dose-dependent effect on [125I]T3 uptake but reduced [125I]T4 uptake by 45% ( P < 0.05) at each concentration tested. Neither the presence of 20 mM K+ nor the presence of low Ca2+ in the medium affected [125I]T3 uptake. In conclusion, the inhibitory effects of Ca2+ channel blockers on T3 uptake in cardiomyocytes are not secondary to their effects on Ca2+ influx but, rather, reflect interference with the putative T3 carrier in the plasma membrane.

Phosphatidic acid increases intracellular free Ca2+ and cardiac contractile force

1996 ◽  
Vol 271 (2) ◽  
pp. H651-H659 ◽  
Author(s):  
Y. J. Xu ◽  
V. Panagia ◽  
Q. Shao ◽  
X. Wang ◽  
N. S. Dhalla
Keyword(s):  
Phosphatidic Acid ◽  
Cyclopiazonic Acid ◽  
Left Ventricular ◽  
Cardiac Contraction ◽  
Channel Blockers ◽  
Maximal Increase ◽  
Rat Cardiomyocytes ◽  
Fura 2 ◽  
Adult Rat

Although phosphatidic acid (PA) is mainly formed due to the hydrolysis of phosphatidylcholine by myocardial phospholipase D, its functional significance in the heart is not fully understood. The present study was designed to determine the effects of PA on intracellular free Ca2+ level ([Ca2+]i) in freshly isolated adult rat cardiomyocytes by using fura 2-acextoxmethylester and free fura 2 technique. Addition of PA at concentrations of 1–200 microM produced a concentration-dependent increase in [Ca2+]i from the basal level of 117 +/- 8 nM; maximal increase in [Ca2+]i was 233 +/- 50 nM, whereas median effective concentration (EC50) for PA was 45 +/- 1.2 microM. This increase in [Ca2+]i was abolished by the removal of extracellular Ca2+ with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and was partially attenuated by Ca2+ channel blockers, verapamil or diltiazem. Preincubation of cardiomyocytes with cyclopiazonic acid and thapsigargin or with ryanodine [to deplete sarcoplasmic reticulum (SR) Ca2+] attenuated the PA-induced increase in [Ca2+]i by 66, 37, and 43%, respectively. Furthermore, the response of [Ca2+]i to PA was blunted by 2-nitro-4 carboxyphenylcarbonate, an inhibitor of phospholipase C, but was unaffected by staurosporine, a protein kinase C inhibitor. PA was also observed to induce Ca2+ efflux from the myocytes. In addition, an injection of PA (0.34 microgram/100 g body wt i.v.) in rats produced a significant increase of the left ventricular developed pressure as well as the maximum rates of cardiac contraction and relaxation within 5 min. These data suggest that the PA-induced increase in [Ca2+]i in cardiomyocytes is a consequence of both Ca2+ influx from the extracellular source and Ca2+ release from the intracellular SR stores. Furthermore, these in vitro data suggest the possibility that PA may regulate [Ca2+]i and contractile parameters in the heart.

Rho kinase is involved in Ca2+ entry of rat penile small arteries

2008 ◽  
Vol 294 (4) ◽  
pp. H1923-H1932 ◽  
Author(s):  
Nuria Villalba ◽  
Edgaras Stankevicius ◽  
Ulf Simonsen ◽  
Dolores Prieto
Keyword(s):  
Kinase Inhibitor ◽  
Physiological Activity ◽  
Rho Kinase ◽  
Cyclopiazonic Acid ◽  
Erectile Tissue ◽  
Kinase C ◽  
Adrenoceptor Agonist ◽  
Rho Kinase Inhibitor ◽  
Intracellular Ca ◽  
Penile Arteries

Tonic physiological activity of RhoA/Rho kinase contributes to the maintenance of penile flaccidity through its involvement in the Ca2+ sensitization of erectile tissue smooth muscle. The present study hypothesized that Rho kinase is also involved in the modulation of Ca2+ entry induced by α1-adrenoceptor stimulation of penile arteries. Rat penile arteries were mounted in microvascular myographs for simultaneous measurements of intracellular Ca2+ ([Ca2+]i) and force. The Rho-kinase inhibitor Y-27632 markedly reduced norepinephrine-mediated electrically induced contractions and the increases in both [Ca2+]i and tension elicited by the α1-adrenoceptor agonist phenylephrine (Phe). In contrast, the protein kinase C (PKC) inhibitor Ro-31-8220 reduced tension without altering the Phe-induced increase in [Ca2+]i. In the presence of nifedipine, Y-27632 still inhibited the non-L-type Ca2+ signal and blunted Phe contraction. Y-27632 did not impair the capacitative Ca2+ entry evoked by store depletion with cyclopiazonic acid but largely reduced the Ba2+ influx stimulated by Phe in fura-2 AM-loaded arteries. The addition of Y-27632 to arteries depolarized with high KCl markedly reduced tension without changing [Ca2+]i. In α-toxin-permeabilized penile arteries stimulated with threshold Ca2+ concentrations, Y-27632 inhibited the sensitization induced by either guanosine 5′- O-(3-thiotriphosphate) (GTPγS) or Phe in the presence of GTPγS. However, Y-27632 failed to alter contractions induced by a maximal concentration of free Ca2+. These results suggest that Rho kinase, besides its contribution to the Ca2+ sensitization of the contractile proteins, is also involved in the regulation of Ca2+ entry through a nonselective cation channel activated by α1-adenoceptor stimulation in rat penile arteries.

Involvement of intracellular Ca2+ stores in inhibitory effects of NO donor SIN-1 and cGMP

1998 ◽  
Vol 275 (1) ◽  
pp. G159-G168
Author(s):  
Hartmut Franck ◽  
Martin Storr ◽  
Andreas Puschmann ◽  
Volker Schusdziarra ◽  
Hans-Dieter Allescher
Keyword(s):  
Response Curve ◽  
Cyclopiazonic Acid ◽  
Inhibitory Effect ◽  
Repetitive Stimulation ◽  
Bay K 8644 ◽  
Inhibitory Effects ◽  
No Donor ◽  
Intracellular Ca ◽  
The Right

We investigated the role of K+ channels and intracellular Ca2+ stores in the relaxations induced by the NO donor 3-morpholinosydnonimine (SIN-1) and 8-bromo-cGMP (8-BrcGMP), 8-(4-chlorophenylthio)-cGMP (pCPT-cGMP), and α,β-methylene-ATP in isolated segments of rat ileum. The inhibitory responses to SIN-1 and the cGMP analogs were not influenced by the K+ blockers apamin, charybdotoxin, iberiotoxin, or glibenclamide, whereas relaxations induced by α,β-methylene-ATP were abolished by apamin and tetraethylammonium. The NO-donor SIN-1 and the cGMP analogs were able to inhibit contractions induced by activation of L-type Ca2+ channels (BAY-K-8644), by carbachol (CCh), and by cyclopiazonic acid (CPA), a blocker of sarcoplasmic Ca2+-ATPase. However, the inhibition of the combined CPA and CCh response was reduced and the dose-response curve of SIN-1 shifted to the right. Intracellular Ca2+ stores were emptied by incubation in Ca2+-free buffer and repetitive stimulation with CCh or BAY-K-8644. After restoration of extracellular Ca2+, the inhibitory effect of SIN-1 and pCPT-cGMP was only attenuated, whereas in the additional presence of CPA, the inhibitory effect of SIN-1 was blocked and the effect of 8-BrcGMP reduced. Thus depleting intracellular Ca2+ stores attenuated the effect of SIN-1 and 8-BrcGMP, suggesting an involvement of functional Ca2+ stores.

scholarly journals IP3R1 regulates Ca2+ transport and pyroptosis through the NLRP3/Caspase-1 pathway in myocardial ischemia/reperfusion injury

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Guixi Mo ◽  
Xin Liu ◽  
Yiyue Zhong ◽  
Jian Mo ◽  
Zhiyi Li ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Cell Model ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Caspase 1 ◽  
Intracellular Ca ◽  
Myocardial Ischemia Reperfusion

AbstractIntracellular ion channel inositol 1,4,5-triphosphate receptor (IP3R1) releases Ca2+ from endoplasmic reticulum. The disturbance of IP3R1 is related to several neurodegenerative diseases. This study investigated the mechanism of IP3R1 in myocardial ischemia/reperfusion (MI/R). After MI/R modeling, IP3R1 expression was silenced in myocardium of MI/R rats to explore its role in the concentration of myocardial enzymes, infarct area, Ca2+ level, NLRP3/Caspase-1, and pyroptosis markers and inflammatory factors. The adult rat cardiomyocytes were isolated and cultured to establish hypoxia/reperfusion (H/R) cell model. The expression of IP3R1 was downregulated or ERP44 was overexpressed in H/R-induced cells. Nifedipine D6 was added to H/R-induced cells to block Ca2+ channel or Nigericin was added to activate NLRP3. IP3R1 was highly expressed in myocardium of MI/R rats, and silencing IP3R1 alleviated MI/R injury, reduced Ca2+ overload, inflammation and pyroptosis in MI/R rats, and H/R-induced cells. The binding of ERP44 to IP3R1 inhibited Ca2+ overload, alleviated cardiomyocyte inflammation, and pyroptosis. The increase of intracellular Ca2+ level caused H/R-induced cardiomyocyte pyroptosis through the NLRP3/Caspase-1 pathway. Activation of NLRP3 pathway reversed the protection of IP3R1 inhibition/ERP44 overexpression/Nifedipine D6 on H/R-induced cells. Overall, ERP44 binding to IP3R1 inhibits Ca2+ overload, thus alleviating pyroptosis and MI/R injury.

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.

Sign in / Sign up

Export Citation Format

Share Document