scholarly journals Depolarization-contraction coupling in short frog muscle fibers. A voltage clamp study.

1984 ◽  
Vol 84 (1) ◽  
pp. 133-154 ◽  
Author(s):  
C Caputo ◽  
F Bezanilla ◽  
P Horowicz
Keyword(s):  
Muscle Fibers ◽  
Tension Development ◽  
Contraction Coupling ◽  
Maximum Tension ◽  
Peak Tension ◽  
Relaxation Phase ◽  
Time To Peak ◽  
Intracellular Ca ◽  
Charge Movements ◽  
Internal Potential

Short muscle fibers (1.5 mm) were dissected from hindlimb muscles of frogs and voltage clamped with two microelectrodes to study phenomena related to depolarization-contraction coupling. Isometric myograms obtained in response to depolarizing pulses of durations between 10 and 500 ms and amplitudes up to 140 mV had the following properties. For suprathreshold pulses of fixed duration (in the range of 20-100 ms), the peak tension achieved, the time to peak tension, and contraction duration increased as the internal potential was made progressively more positive. Peak tension eventually saturates with increasing internal potentials. For pulse durations of greater than or equal to 50 ms, the rate of tension development becomes constant for increasing internal potentials when peak tensions become greater than one-third of the maximum tension possible. Both threshold and maximum steepness of the relation between internal potential and peak tension depend on pulse duration. The relation between the tension-time integral and the stimulus amplitude-duration product was examined. The utility of this relation for excitation-contraction studies is based on the observation that once a depolarizing pulse configuration has elicited maximum tension, further increases in either stimulus duration or amplitude only prolong the contractile response, while the major portion of the relaxation phase after the end of a pulse is exponential, with a time constant that is not significantly affected by either the amplitude or the duration of the pulse. Hence, the area under the tension-response curve provides a measure of the availability to troponin of the calcium released from the sarcoplasmic reticulum in response to membrane depolarization. The results from this work complement those obtained in experiments in which intramembrane charge movements related to contractile activation were studied and those in which intracellular Ca++ transients were measured.

Effect of hypoxia on mechanical function in the neonatal mammalian heart

1978 ◽  
Vol 235 (5) ◽  
pp. H469-H474 ◽  
Author(s):  
J. M. Jarmakani ◽  
M. Nakazawa ◽  
T. Nagatomo ◽  
G. A. Langer
Keyword(s):  
Glycolytic Pathway ◽  
Mechanical Function ◽  
Maximal Rate ◽  
Half Time ◽  
Perfusion Rate ◽  
Tension Development ◽  
Peak Tension ◽  
Time To Peak ◽  
Newborn Rabbit ◽  
Mammalian Heart

The effect of 30 min of hypoxia followed by reoxygenation on mechanical function was studied in isolated, arterially perfused, neonatal rabbit and dog hearts. All studies were performed at a perfusion rate of 2.5 ml/g-min, at a pacing rate of 60 beats/min and at 27 degrees C. The muscles were perfused with Krebs-Henseleit solutions equilibrated with 95% O2 and 5% CO2 (control) or 95% N2 and 5% CO2 (hypoxia). In the newborn rabbit and dog, both the developed tension (DT) and the maximal rate of tension development (dT/dtmax+) decreased during the first 3 min of hypoxia and then recovered to values not different from control. The effect of hypoxia on DT and dT/dtmax+ was inversely related to age in both the rabbit and dog. The equations describing the decline in DT and dT/dTmax+ during hypoxia and the recovery during reoxygenation were best expressed by two or three exponentials. Time to peak tension and half time to relaxation decreased during hypoxia and the decrease was also inversely related to age. The fact that the newborn was able to maintain normal mechanical function during hypoxia suggests that the newborn is capable of maintaining normal myocardial ATP levels due to enhanced flux through the glycolytic pathway.

Chronic verapamil treatment attenuates the negative inotropic effect of ethanol in diabetic rat myocardium

1994 ◽  
Vol 72 (9) ◽  
pp. 1013-1018 ◽  
Author(s):  
Ricardo A. Brown ◽  
Prashant Bhasin ◽  
Adedapo O. Savage ◽  
Joseph C. Dunbar
Keyword(s):  
Negative Inotropic Effect ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Diabetic Rat ◽  
Tension Development ◽  
Altered Expression ◽  
Peak Tension ◽  
Time To Peak ◽  
Diabetic Myocardium

It is well established that cardiomyopathy is a consistent feature of diabetic myocardium and that alcohol consumption increases the risk of cardiovascular disease among diabetic subjects. The objective of this investigation was to determine whether acute or chronic verapamil treatment attenuates the negative inotropic effect of ethanol (EtOH) in the diabetic rat heart. Wistar rats were made diabetic with streptozotocin (55 mg/kg, iv). Left-ventricular papillary muscles, from normal and diabetic (8 weeks) rats, were superfused with Tyrode's solution at 30 °C while driven at 0.5 Hz. A subgroup of diabetic and normal animals received daily injections of verapamil (8 mg/kg, ip; 8 weeks), whereas muscles from untreated animals were exposed to verapamil (2 μM) in vitro. Peak tension developed (PTD), time to peak tension (TPT), time to 90% relaxation (RT90), and the maximum velocities of tension development (+VT) and decay (−VT) were determined in the absence and presence of clinically relevant concentrations of EtOH (80–240 mg/dL, i.e., 17.4–52.1 mM). Ethanol at 80 mg/dL reduced PTD, + VT, and −VT only in preparations from diabetic animals. Higher concentrations of EtOH (120–240 mg/dL) decreased PTD, TPT, +VT, and −VT. The negative inotropic effect of EtOH (240 mg/dL) was attenuated only in diabetic myocardium chronically treated with verapamil, whereas acute verapamil treatment potentiated the negative inotropic effect of EtOH in both normal and diabetic myocardium. Thus, chronic verapamil therapy diminishes the negative inotropic effect of EtOH in diabetic myocardium and acute verapamil treatment exaggerates it. Altered expression of membrane-bound calcium channels may be involved in the negative inotropic response to EtOH in long-term diabetes.Key words: ethanol, papillary muscle, inotropism, myocardium, force of contraction, diabetes mellitus.

The effect of temperature on the tension responses of the anterior byssal retractor muscle (abrm) of Mytilus edulis

1982 ◽  
Vol 97 (1) ◽  
pp. 375-384
Author(s):  
C. M. Linehan
Keyword(s):  
Ambient Temperature ◽  
Latent Period ◽  
Mytilus Edulis ◽  
Effect Of Temperature ◽  
Retractor Muscle ◽  
Tension Development ◽  
Maximum Tension ◽  
Peak Tension ◽  
The Relationship ◽  
Anterior Byssal Retractor Muscle

The effect of ambient temperature on the response of the ABRM of Mytilus edulis to acetylcholine and 5-hydroxytryptamine has been examined. As the ambient temperature was increased, the latent period and the maximum tension developed decreased while the rate of tension development and the rate of relaxation increased. The relationship between temperature and the rate of tension development showed three distinct linear phases from 2–25, 25-35 and 35-45 degrees C. The reduction in peak tension with temperature could also be resolved into three portions from 2–25, 25-40 and above 40 degrees C. As the temperature was increased above approximately 27 degrees C the rate of relaxation in the absence of 5-HT approached the rate of relaxation in the presence of 5-HT. The significance of these results and possible explanations for them are considered.

Calcium fluxes and contractility in isolated guinea pig atrium: effect of A23187

1978 ◽  
Vol 235 (1) ◽  
pp. C13-C19 ◽  
Author(s):  
D. R. Holland ◽  
W. M. Armstrong ◽  
M. I. Steinberg
Keyword(s):  
Guinea Pig ◽  
Myocardial Cell ◽  
Ionophore A23187 ◽  
Inotropic Action ◽  
Tension Development ◽  
Peak Tension ◽  
Time To Peak ◽  
Endogenous Histamine ◽  
Resultant Increase ◽  
45Ca Efflux

The Ca2+ ionophore A23187 (10(-6) to 3 X 10(-5) M) increased the force of contraction is isolated guinea pig atria. In individual twitches, peak tension, maximum rate of tension development, time to peak tension, and total twitch duration were all increased by A23187. Tripelennamine, indomethacin, and atropine did not significantly alter the inotropic effect of A23187. Serotonin produced changes in individual twitches that differed qualitatively and quantitatively from those of A23187. Therefore, the inotropic action of A23187 is probably not mediated by release of endogenous histamine, prostaglandins, acetylcholine, or serotonin. 45Ca influx and efflux were increased by A23187. The enhanced 45Ca efflux exceeded that which would be predicted if the ionophore acted only to increase the passive Ca2+ permeability of the myocardial cell membrane. These results suggest that A23187 facilitates the entry of extracellular Ca2+ into the myocardial cell and the release of intracellular Ca2+ stores into the myoplasm. The resultant increase in intracellular Ca2+ activity could account for the positive inotropic action of A23187.

scholarly journals Phenol increases intracellular [Ca2+] during twitch contractions in intact Xenopus skeletal myofibers

2010 ◽  
Vol 109 (5) ◽  
pp. 1384-1393 ◽  
Author(s):  
Leonardo Nogueira ◽  
Michael C. Hogan
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Muscle Function ◽  
Ryanodine Receptors ◽  
Muscle Fibers ◽  
Muscle Contractility ◽  
Tension Development ◽  
Low Concentrations ◽  
Intact Muscle ◽  
Intracellular Ca

Phenol is a neurolytic agent used for management of spasticity in patients with either motoneuron lesions or stroke. In addition, compounds that enhance muscle contractility (i.e., polyphenols, etc.) may affect muscle function through the phenol group. However, the effects of phenol on muscle function are unknown, and it was, therefore, the purpose of the present investigation to examine the effects of phenol on tension development and Ca2+ release in intact skeletal muscle fibers. Dissected intact muscle fibers from Xenopus laevis were electrically stimulated, and cytosolic Ca2+ concentration ([Ca2+]c) and tension development were recorded. During single twitches and unfused tetani, phenol significantly increased [Ca2+]c and tension without affecting myofilament Ca2+ sensitivity. To investigate the phenol effects on Ca2+ channel/ryanodine receptors, single fibers were treated with different concentrations of caffeine in the presence and absence of phenol. Low concentrations of phenol significantly increased the caffeine sensitivity ( P < 0.01) and reduced the caffeine concentrations necessary to produce nonstimulated contraction (contracture). However, at high phenol concentrations, caffeine did not increase tension or Ca2+ release. These results suggest that phenol affects the ability of caffeine to release Ca2+ through an effect on the ryanodine receptors, or on the sarcoplasmic reticulum Ca2+ pump. During tetanic contractions inducing fatigue, phenol application decreased the time to fatigue. In summary, phenol increases intracellular [Ca2+] during twitch contractions in muscle fibers without altering myofilament Ca2+ sensitivity and may be used as a new agent to study skeletal muscle Ca2+ handling.

scholarly journals Expression of active p21-activated kinase-1 induces Ca2+flux modification with altered regulatory protein phosphorylation in cardiac myocytes

2009 ◽  
Vol 296 (1) ◽  
pp. C47-C58 ◽  
Author(s):  
Katherine A. Sheehan ◽  
Yunbo Ke ◽  
Beata M. Wolska ◽  
R. John Solaro
Keyword(s):  
Troponin I ◽  
Ventricular Myocytes ◽  
Regulatory Protein ◽  
Cardiac Contractility ◽  
Tension Development ◽  
Cell Shortening ◽  
Time To Peak ◽  
Fiber Tension ◽  
Intracellular Ca ◽  
P21 Activated Kinase

p21-Activated kinase-1 (Pak1) is a serine-threonine kinase that associates with and activates protein phosphatase 2A in adult ventricular myocytes and, thereby, induces increased Ca2+sensitivity of skinned-fiber tension development mediated by dephosphorylation of myofilament proteins (Ke Y, Wang L, Pyle WG, de Tombe PP, Solaro RJ. Circ Res 94: 194–200, 2004). We test the hypothesis that activation of Pak1 also moderates cardiac contractility through regulation of intracellular Ca2+fluxes. We found no difference in field-stimulated intracellular Ca2+concentration ([Ca2+]i) transient amplitude and extent of cell shortening between myocytes expressing constitutively active Pak1 (CA-Pak1) and controls expressing LacZ; however, time to peak shortening was significantly faster and rate of [Ca2+]idecay and time of relengthening were slower. Neither caffeine-releasable sarcoplasmic reticulum (SR) Ca2+content nor fractional release was different in CA-Pak1 myocytes compared with controls. Isoproterenol application revealed a significantly blunted increase in [Ca2+]itransient amplitude, as well as a slowed rate of [Ca2+]idecay, increased SR Ca2+content, and increased cell shortening, in CA-Pak1 myocytes. We found no significant change in phospholamban phosphorylation at Ser16or Thr17in CA-Pak1 myocytes. Analysis of cardiac troponin I revealed a significant reduction in phosphorylated species that are primarily attributable to Ser23/24in CA-Pak1 myocytes. Nonstimulated, spontaneous SR Ca2+release sparks were significantly smaller in amplitude in CA-Pak1 than LacZ myocytes. Propagation of spontaneous Ca2+waves resulting from SR Ca2+overload was significantly slower in CA-Pak1 myocytes. Our data indicate that CA-Pak1 expression has significant effects on ventricular myocyte contractility through altered myofilament Ca2+sensitivity and modification of the [Ca2+]itransient.

Influence of overload on recovery of rat plantaris from partial denervation

1989 ◽  
Vol 66 (2) ◽  
pp. 732-740 ◽  
Author(s):  
R. N. Michel ◽  
P. F. Gardiner
Keyword(s):  
Muscle Fibers ◽  
Motor Units ◽  
Surgical Removal ◽  
Plantaris Muscle ◽  
Cross Sectional ◽  
Peak Tension ◽  
Time To Peak ◽  
Partial Denervation ◽  
Whole Muscle ◽  
Tetanic Tension

A functional index of neural adaptability is the capacity of motoneurons to extend and establish supernumerary connections with neighboring denervated muscle fibers. The purpose of this study was to guage this response in rat plantaris muscles subjected to increased levels of activity resulting from the surgical removal of the synergistic gastrocnemius and soleus muscles. Thirty-seven days of overload increased plantaris absolute (69%) and relative (82%) weight, whole muscle (35%) and individual fiber (37%) mean cross-sectional area, half-relaxation time (1/2RT; 25%), and maximum tetanic tension (P0; 21%). In a separate group of animals that had undergone 30 days of overload, three-quarters of the plantaris muscle fibers were denervated by sectioning radicular nerve L4. At 7 days postlesion, contractile responses were obtained from sprouting motor units remaining in radicular nerve L5, and the results compared to a nonoverloaded group that had undergone this same procedure. Twitch time to peak tension and 1/2RT were prolonged in normal partially denervated (PD) and overloaded partially denervated (OPD) muscles, and this response was significantly greater in the overloaded muscles. Both PD and OPD muscles increased twitch tension (38%) and peak tension developed at 25 Hz (34%) to a similar extent, during recovery from partial denervation. These increases, attributable to sprouting of L5 motor axon collaterals, were matched in PD muscles with a corresponding increase in P0, a response which did not occur in OPD muscles. Additionally, a more extensive decrease in P0 occurred as a result of partial denervation in OPD muscles compared with whole muscle P0 of nondenervated muscle (L4 plus L5 stimulation).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Active State in Heart Muscle

1967 ◽  
Vol 50 (3) ◽  
pp. 661-676 ◽  
Author(s):  
Edmund H. Sonnenblick
Keyword(s):  
Heart Muscle ◽  
Mechanical Response ◽  
Electrical Stimulus ◽  
Isometric Tension ◽  
Maximum Intensity ◽  
Active State ◽  
Tension Development ◽  
Peak Tension ◽  
Time To Peak ◽  
Time Required

The course of active state in heart muscle has been analyzed using a modified quick release method. The onset of maximum active state was found to be delayed, requiring 110–500 msec from time of stimulation, while the time to peak isometric tension required 250–650 msec. Further, the time from stimulation to peak tension was linearly related to the time required to establish maximum intensity of active state as well as to the duration of maximum active state. The duration of maximum active state was prolonged (90–220 msec), occupying most of the latter half of the rising phase of the isometric contraction. Norepinephrine (10-5 M) shortened the latency from electrical stimulus to mechanical response, accelerated the onset of maximum active state, increased its intensity, decreased its duration, and accelerated its rate of decline. These changes were accompanied by an increase in the rate of tension development and the tension developed while the time from stimulation to peak isometric tension was abbreviated. Similar findings were shown for strophanthidin (1 µg/ml) although lesser decrements in the duration of maximum active state and time to peak tension were found than with norepinephrine for similar increments in the maximum intensity of active state.

scholarly journals Effect of membrane polarization on contractile threshold and time course of prolonged contractile responses in skeletal muscle fibers.

1984 ◽  
Vol 84 (6) ◽  
pp. 927-943 ◽  
Author(s):  
C Caputo ◽  
P Bolaños ◽  
G F Gonzalez
Keyword(s):  
Membrane Potential ◽  
Time Course ◽  
Muscle Fibers ◽  
Fiber Membrane ◽  
Activation Curve ◽  
Contractile Responses ◽  
Membrane Polarization ◽  
Peak Tension ◽  
Relaxation Phase ◽  
Ringer’S Solution

Short muscle fibers (less than 1.5 mm) from the m. lumbricalis IV digiti of Rana pipiens were voltage-clamped at -100 mV with a two-microelectrode technique, in normal Ringer's solution containing 10(-6) g/ml tetrodotoxin. The activation curve relating peak tension to membrane potential could be shifted toward more negative or less negative potential values by hyperpolarizing or depolarizing the fiber membrane to -130, -120, or -70 mV, respectively, which indicates that contractile threshold depends on the fiber membrane potential. Long (greater than 5 s) depolarizing (90 mV) pulses induce prolonged contractile responses showing a plateau and a rapid relaxation phase similar to K contractures. Conditioning hyperpolarizations prolong the time course of these responses, while conditioning depolarizations shorten it. The shortening of the response time course, which results in a decrease of the area under the response, is dependent on the amplitude and duration of the conditioning depolarization. Depending on the magnitude and duration, a conditioning depolarization may also reduce peak tension. When the area under the response is reduced by 50%, the level of membrane potential also affects the repriming rate. During repriming, peak tension is restored before the contracture area. Thus, when peak tension is reprimed to 80%, the area is reprimed by 50% of its normal value. Repriming has a marked temperature dependency with a Q10 higher than 4. These results are compatible with the idea that an inactivation process, voltage and time dependent, regulates the release of calcium from the sarcoplasmic reticulum during these responses.

scholarly journals Altered inotropic response to IGF-I in diabetic rat heart: influence of intracellular Ca2+and NO

1998 ◽  
Vol 275 (3) ◽  
pp. H823-H830 ◽  
Author(s):  
Jun Ren ◽  
Mary F. Walsh ◽  
Marwan Hamaty ◽  
James R. Sowers ◽  
Ricardo A. Brown
Keyword(s):  
Methyl Ester ◽  
Left Ventricular ◽  
Contractile Properties ◽  
Inotropic Response ◽  
Tension Development ◽  
Time To Peak ◽  
Igf I ◽  
Intracellular Ca ◽  
Dose Dependent Increase ◽  
Dose Dependent

Normally, insulin-like growth factor I (IGF-I) exerts positive effects on cardiac growth and myocardial contractility, but resistance to its action has been reported in diabetes. This study was designed to determine whether IGF-I-induced myocardial contractile action is altered in diabetes as a result of an intrinsic alteration of contractile properties at the cellular level. Contractile responses to IGF-I were examined in left ventricular papillary muscles and ventricular myocytes from normal and short-term (5–7 days) streptozotocin-induced diabetic rats. Mechanical properties of muscles and myocytes were evaluated using a force transducer and an edge detector, respectively. Preparations were electrically stimulated at 0.5 Hz, and contractile properties analyzed include peak tension development (PTD) or peak twitch amplitude (PTA), time to peak contraction/shortening, and time to 90% relaxation/relengthening. Intracellular Ca2+ transients were measured as fura 2 fluorescence intensity changes. IGF-I (1–500 ng/ml) caused a dose-dependent increase in PTD and PTA in preparations from normal but not diabetic animals. IGF-I did not alter time to peak contraction/shortening or time to 90% relaxation/relengthening. Pretreatment with the NO synthase inhibitor N ω-nitro-l-arginine methyl ester (100 μM) attenuated IGF-I-induced increases in PTD in normal myocardium but unmasked a positive inotropic action in diabetic animals. Pretreatment with N ω-nitro-l-arginine methyl ester blocked IGF-I-induced increases in PTA in single myocytes. Consistent with its inotropic actions on muscles and myocytes, IGF-I induced a dose-dependent increase in Ca2+transients in normal but not diabetic myocytes. These results suggest that the IGF-I-induced inotropic response is depressed in diabetes because of an intrinsic alteration at the myocyte level. Mechanisms underlying this alteration in IGF-I-induced myocardial response may be related to changes in intracellular Ca2+ and/or NO production in diabetes.

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