scholarly journals Minor role of a Ca2+-depleted sarcoplasmic reticulum in heterologous desensitization of smooth muscle to K+

1998 ◽  
Vol 275 (4) ◽  
pp. C1095-C1103 ◽  
Author(s):  
Robert L. Wardle ◽  
Richard A. Murphy
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Cyclopiazonic Acid ◽  
Minor Role ◽  
Large Reduction ◽  
Atpase Inhibitor ◽  
Before And After ◽  
Heterologous Desensitization ◽  
Porcine Carotid Artery

Exposure of porcine carotid artery smooth muscle (PCASM) to histamine was followed by a large reduction in the rate of force generation in response to 40 mM KCl. This was shown to be a manifestation of slow attainment of a steady-state myoplasmic Ca2+concentration ([Ca2+]i). We hypothesized that if net transsarcolemmal Ca2+ flux into the depolarized PCASM cells is the same before and after a desensitizing histamine treatment, then the transient attenuation of the increase in [Ca2+]imay be due to accelerated uptake of Ca2+ by a partially depleted sarcoplasmic reticulum (SR) acting as a Ca2+ sink or superficial buffer barrier. We tested this hypothesis by eliciting responses of “desensitized PCASM” to 40 mM KCl in the presence of cyclopiazonic acid (CPA), an SR Ca2+-ATPase inhibitor. Contractions of CPA-treated tissues were attenuated less than those of tissues not treated with CPA, but they were not abolished. CPA-insensitive mechanism(s) dominated the desensitization. We conclude that histamine pretreatment reduced net transsarcolemmal Ca2+ flux into PCASM in response to 40 mM KCl.

Spontaneous electrical rhythmicity and the role of the sarcoplasmic reticulum in the excitability of guinea pig gallbladder smooth muscle cells

2006 ◽  
Vol 290 (4) ◽  
pp. G655-G664 ◽  
Author(s):  
Onesmo B. Balemba ◽  
Matthew J. Salter ◽  
Thomas J. Heppner ◽  
Adrian D. Bonev ◽  
Mark T. Nelson ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Action Potentials ◽  
Cyclopiazonic Acid ◽  
Cellular Mechanisms ◽  
Voltage Dependent ◽  
Spontaneous Action ◽  
Potential Activity ◽  
Spontaneous Action Potentials

Spontaneous action potentials and Ca2+ transients were investigated in intact gallbladder preparations to determine how electrical events propagate and the cellular mechanisms that modulate these events. Rhythmic phasic contractions were preceded by Ca2+ flashes that were either focal (limited to one or a few bundles), multifocal (occurring asynchronously in several bundles), or global (simultaneous flashes throughout the field). Ca2+ flashes and action potentials were abolished by inhibiting sarcoplasmic reticulum (SR) Ca2+ release via inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3] channels with 2-aminoethoxydiphenyl borate and xestospongin C or by inhibiting voltage-dependent Ca2+ channels (VDCCs) with nifedipine or diltiazem or nisoldipine. Inhibiting ryanodine channels with ryanodine caused multiple spikes superimposed upon plateaus of action potentials and extended quiescent periods. Depletion of SR Ca2+ stores with thapsigargin or cyclopiazonic acid increased the frequency and duration of Ca2+ flashes and action potentials. Acetylcholine, carbachol, or cholecystokinin increased synchronized and increased the frequency of Ca2+ flashes and action potentials. The phospholipase C (PLC) inhibitor U-73122 did not affect Ca2+ flash or action potential activity but inhibited the excitatory effects of acetylcholine on these events. These results indicate that Ca2+ flashes correspond to action potentials and that rhythmic excitation in the gallbladder is multifocal among gallbladder smooth muscle bundles and can be synchronized by excitatory agonists. These events do not depend on PLC activation, but agonist stimulation involves activation of PLC. Generation of these events depends on Ca2+ entry via VDCCs and on Ca2+ mobilization from the SR via Ins(1,4,5)P3 channels.

Mechanisms of cyclic nucleotide-induced relaxation in canine tracheal smooth muscle

1995 ◽  
Vol 268 (3) ◽  
pp. L407-L413 ◽  
Author(s):  
I. McGrogan ◽  
S. Lu ◽  
S. Hipworth ◽  
L. Sormaz ◽  
R. Eng ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cyclic Nucleotide ◽  
Cyclopiazonic Acid ◽  
Inhibitory Effect ◽  
Beta Agonist ◽  
Cyclic Monophosphate ◽  
Median Effective Concentration ◽  
Camp Levels ◽  
Ca2 Channels

The effects of exogeneous cyclopiazonic acid (CPA, 10 microM), a selective inhibitor of the sarcoplasmic reticulum (SR) Ca2+ adenosinetriphosphatase, on cyclic nucleotide-induced relaxations of canine airway smooth muscle were examined. Strips of tracheal muscle were precontracted with carbachol (50% median effective concentration, 0.1 microM) or with 60 mM KCl. The beta-agonist isoproterenol (ISO, 10 microM) relaxed the tissue by approximately 50%. The relaxation was reduced in the presence of CPA when L-type Ca2+ channels were available but not when these were blocked by 0.1 microM nifedipine. Forskolin (1.0 microM), an adenylate cyclase activator, was less effective at inhibiting the contraction than ISO, and addition of CPA did not block its inhibitory effect as effectively as when ISO was used. Radioimmunoassay indicated that both these agents raised adenosine 3',5'-cyclic monophosphate (cAMP) levels to the same degree. Very little relaxation of the precontracted smooth muscle was elicited by 3 mM 8-bromo-adenosine 3',5'-cyclic monophosphate (8-BrcAMP), and addition of CPA had no effect. Sodium nitroprusside (100 microM) and 8-bromo-guanosine 3',5'-cyclic monophosphate (10 mM) inhibited contraction to a greater degree than any agent that raised cAMP. These inhibitions were greatly reduced in the presence of CPA when L-type Ca2+ channels were available. We conclude that pumping of Ca2+ into SR plays a major role guanosine 3',5'-cyclic monophosphate-produced but not cAMP-induced relaxation; L-type Ca2+ channels must be available for the relaxant role of Ca2+ pumping into the SR to be expressed; and ISO-induced relaxation may not involve primarily elevation of the cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of Sarcoplasmic Reticulum in the Contractile Function of Vascular Smooth Muscle as Studied by 2,5-Di-(Tert-Butyl)-1,4-Benzohydroquinone

Neurosignals ◽  
1992 ◽  
Vol 1 (4) ◽  
pp. 182-193 ◽  
Author(s):  
Hiroyuki Shimamoto ◽  
Ingrid L.A. Majarais ◽  
Yoriko Shimamoto ◽  
Chiu-Yin Kwan ◽  
Edwin E. Daniel
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Vascular Smooth Muscle ◽  
Contractile Function ◽  
Tert Butyl

scholarly journals A Theory of the Mechanism of Cerebral Vasospasm and Its Reversal, the Role of Calcium and Cyclic AMP

1976 ◽  
Vol 3 (4) ◽  
pp. 223-226 ◽  
Author(s):  
Eric W. Peterson ◽  
Richard Leblanc
Keyword(s):  
Smooth Muscle ◽  
Subarachnoid Hemorrhage ◽  
Sarcoplasmic Reticulum ◽  
Cyclic Amp ◽  
Smooth Muscle Cell ◽  
Calcium Ion ◽  
Basic Mechanism ◽  
Free Intracellular Calcium ◽  
Intracellular Calcium Ion

SUMMARY:It is proposed that the basic mechanism of vasospasm which sometimes follows subarachnoid hemorrhage is dependent on increased free intracellular calcium ion produced by spasmogens from closely applied extravasated blood. Relaxation of this spasm occurs when the intracellular cyclic AMP levels are raised, resulting in sequestration of calcium ion by the vascular smooth muscle cell sarcoplasmic reticulum.

CGRP and ANF cause relaxation of opossum internal anal sphincter via different mechanisms

1991 ◽  
Vol 260 (5) ◽  
pp. G764-G769 ◽  
Author(s):  
S. Rattan ◽  
C. Moummi ◽  
S. Chakder
Keyword(s):  
Smooth Muscle ◽  
Anal Sphincter ◽  
Cyclic Nucleotides ◽  
Internal Anal Sphincter ◽  
Camp Content ◽  
Calcitonin Gene ◽  
Before And After ◽  
Camp And Cgmp

This investigation examined and compared the role of cyclic nucleotides in the mediation of internal anal sphincter (IAS) relaxation caused by the addition of neuropeptide calcitonin gene-related peptide (CGRP) and atrial natriuretic factor (ANF). The studies were performed in vitro on smooth muscle strips of opossum IAS. The relaxation produced by CGRP and ANF was examined before and after the addition of tetrodotoxin (TTX) (1 x 10(-6)M). At this concentration, TTX did not have any significant effect on the relaxation produced by either CGRP or ANF, suggesting that these peptides act directly on the smooth muscle. Addition of CGRP (3 x 10(-6) M) produced the maximal relaxation and significantly increased cAMP content without changing cGMP. On the other hand, addition of ANF (3 x 10(-6) M) caused a similar fall in IAS tension that was accompanied by a significant elevation in cGMP without any change in cAMP content. The rises in the levels of cyclic nucleotides preceded the onset of fall in the resting tension of IAS. Our results demonstrate that CGRP and ANF relax isolated strips of opossum IAS by their action directly at the smooth muscle and that this relaxation is associated with an increase in cAMP and cGMP, respectively. The studies suggest the presence of both cAMP and cGMP pathways in the IAS and that the relaxation of IAS smooth muscle in response to different peptides may occur via a specific intracellular biochemical pathway.

scholarly journals Sarcoplasmic reticulum and endothelium independently regulate venous smooth muscle [Ca2+]iand contraction

1999 ◽  
Vol 277 (2) ◽  
pp. H749-H755
Author(s):  
Régent Laporte ◽  
Ismail Laher
Keyword(s):  
Smooth Muscle ◽  
Steady State ◽  
Sarcoplasmic Reticulum ◽  
Salt Solution ◽  
Isometric Contraction ◽  
Cyclopiazonic Acid ◽  
Physiological Salt Solution ◽  
Sustained Contraction ◽  
Facial Vein ◽  
State Increase

In rings of rabbit facial vein (RFV), depletion of sarcoplasmic reticulum (SR) Ca2+ by caffeine abolished the subsequent isometric contraction to 25 mM K+ physiological salt solution (25K-PSS). However, the associated steady-state increase of smooth muscle intracellular free Ca2+concentration ([Ca2+]i), measured using fura PE3 and cuvette photometry, was not altered. Treatment with the specific SR Ca2+ pump inhibitor cyclopiazonic acid (30 μM) after caffeine-induced SR Ca2+ depletion restored and greatly augmented the 25K-PSS-induced contraction. This suggests that SR Ca2+ depletion leads to a dissociation of K+-induced [Ca2+]iincrease from contraction that was dependent on Ca2+ pump-mediated SR Ca2+ uptake. Endothelium removal augmented the 25K-PSS-induced [Ca2+]iincrease after caffeine-induced SR Ca2+ depletion. However, this was associated with only a small and transient contraction. Exposure of endothelium-denuded RFV to cyclopiazonic acid after caffeine-induced SR Ca2+ depletion further amplified the 25K-PSS-induced [Ca2+]iincrease, which was associated with a large and sustained contraction. However, the latter [Ca2+]iincrease was still higher than in endothelium-intact RFV. This suggests that the endothelium dampens the [Ca2+]irise associated with K+-induced Ca2+ influx, but independently of Ca2+ pump-mediated SR Ca2+ uptake.

scholarly journals Superficial buffer barrier and preferentially directed release of Ca2+ in canine airway smooth muscle

1999 ◽  
Vol 276 (5) ◽  
pp. L744-L753 ◽  
Author(s):  
Luke J. Janssen ◽  
Pierre A. Betti ◽  
Stuart J. Netherton ◽  
Denise K. Walters
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Airway Smooth Muscle ◽  
Cyclopiazonic Acid ◽  
Membrane Currents ◽  
Global Changes ◽  
Fura 2 ◽  
Mechanical Responses ◽  
Filling State

We examined cytosolic concentration of Ca2+([Ca2+]i) in canine airway smooth muscle using fura 2 fluorimetry (global changes in [Ca2+]i), membrane currents (subsarcolemmal [Ca2+]i), and contractions (deep cytosolic [Ca2+]i). Acetylcholine (10−4 M) elicited fluorimetric, electrophysiological, and mechanical responses. Caffeine (5 mM), ryanodine (0.1–30 μM), and 4-chloro-3-ethylphenol (0.1–0.3 mM), all of which trigger Ca2+-induced Ca2+ release, evoked Ca2+ transients and membrane currents but not contractions. The sarcoplasmic reticulum (SR) Ca2+-pump inhibitor cyclopiazonic acid (CPA; 10 μM) evoked Ca2+transients and contractions but not membrane currents. Caffeine occluded the response to CPA, whereas CPA occluded the response to acetylcholine. Finally, KCl contractions were augmented by CPA, ryanodine, or saturation of the SR and reduced when SR filling state was decreased before exposure to KCl. We conclude that 1) the SR forms a superficial buffer barrier dividing the cytosol into functionally distinct compartments in which [Ca2+]iis regulated independently; 2) Ca2+-induced Ca2+ release is preferentially directed toward the sarcolemma; and 3) there is no evidence for multiple, pharmacologically distinct Ca2+ pools.

Role of plasma membrane Ca2+-ATPase in contraction-relaxation processes of the bladder: evidence from PMCA gene-ablated mice

2006 ◽  
Vol 290 (4) ◽  
pp. C1239-C1247 ◽  
Author(s):  
Li Liu ◽  
Yukisato Ishida ◽  
Gbolahan Okunade ◽  
Gary E. Shull ◽  
Richard J. Paul
Keyword(s):  
Smooth Muscle ◽  
Plasma Membrane ◽  
Cyclopiazonic Acid ◽  
Physiological Salt Solution ◽  
Relaxation Processes ◽  
Half Time ◽  
Bladder Smooth Muscle ◽  
Gene Manipulation ◽  
Smooth Muscle Contractility

We investigated the roles and relationships of plasma membrane Ca2+-ATPase (PMCA), sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2, and Na+/Ca2+ exchanger (NCX) in bladder smooth muscle contractility in Pmca-ablated mice: Pmca4-null mutant ( Pmca4 −/−) and heterozygous Pmca1 and homozygous Pmca4 double gene-targeted ( Pmca1 +/− Pmca4 −/−) mice. Gene manipulation did not alter the amounts of PMCA1, SERCA2, and NCX. To study the role of each Ca2+ transport system, contraction of circular ring preparations was elicited with KCl (80 mM) plus atropine, and then the muscle was relaxed with Ca2+-free physiological salt solution containing EGTA. We measured the contributions of Ca2+ clearance components by inhibiting SERCA2 (with 10 μM cyclopiazonic acid) and/or NCX (by replacing NaCl with N-methyl-d-glucamine/HCl plus 10 μM KB-R7943). Contraction half-time (time to 50% of maximum tension) was prolonged in the gene-targeted muscles but marginally shortened when SERCA2 or NCX was inhibited. The inhibition of NCX significantly inhibited this prolongation, suggesting that NCX activity might be augmented to compensate for PMCA4 function in the gene-targeted muscles under nonstimulated conditions. Inhibition of SERCA2 and NCX as well as gene targeting all prolonged the relaxation half-time. The contribution of PMCA to relaxation was calculated to be ∼25–30%, with that of SERCA2 being 20% and that of NCX being 70%. PMCA and SERCA2 appeared to function additively, but the function of NCX might overlap with those of other components. In summary, gene manipulation of PMCA indicates that PMCA, in addition to SERCA2 and NCX, plays a significant role in both excitation-contraction coupling and the Ca2+ extrusion-relaxation relationship, i.e., Ca2+ homeostasis, of bladder smooth muscle.

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