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Query: KEGG:D01453 (caffeine)
 21,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. A method for producing rapid [Ca2+] and [Sr2+] changes in the frog skinned muscle fibre preparation while maintaining constant all other cationic concentrations (Moisescu, 1976a, b) is described and analysed in detail. 2. Different experiments, some of them involving the Ca2+-sensitive photoprotein aequorin, as well as theoretical considerations, indicate that with this method one can produce a Ca2+ (or Sr2+) concentration change within 0.1--0.15 sec in a whole preparation having a diameter of 50 micrometer. 3. The rate of force development was similar to that observed in vivo. 4. The radial diffusion coefficient of EGTA in relaxed myofibrillar preparations was measured and found to be 4.6 x 10(-6) cm2sec-1 at 20 degrees C. 5. The sarcoplasmic reticulum in myofibrillar bundles was found to be active with respect to both Ca2+ and Sr2+ in the solutions used ([Mg2+] 1 mM; [Na] 30 mM; [K] 140-170 mM; [Cl] less than or equal to 20 mM; pH 7.10). 6. The amount of Ca released by caffeine from internal stores (previously loaded with Ca) can raise the total Ca concentration in the muscle fibre preparation by at least 1.8 mM. 7. The presence of 10 mM-caffeine in all bathing solutions reduced drastically the ability of the sarcoplasmic reticulum to accumulate both Ca and Sr.
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PMID:Calcium and strontium concentration changes within skinned muscle preparations following a change in the external bathing solution. 2 36

The subcellular mechanisms of twitch-force potentiation with paired electrical stimulation was studied in ferret ventricular myocardium using the bioluminescent calcium indicator aequorin. It is demonstrated for the first time that interpolation of an extrasystole in a train of conditioned twitches results in a beat-to-beat change in [Ca2+]i and force. Steady-state twitch force and Ca2+i were increased with paired stimulation. Increased [Ca2+]o in the setting of paired stimulation resulted in an increase in the amplitude of the postextrasystole and associated Ca2+ transient. Verapamil, a Ca2+ channel antagonist, had the opposite effect of increased [Ca2+]o. Postextrasystole potentiation was still present, but diminished in amplitude. These results indicate that postextrasystole potentiation is in part due to a verapamil-depletable store (Ca2+). Postextrasystole potentiation is therefore predominantly dependent on sarcoplasmic reticulum (SR) Ca2+ loading. Ryanodine, an alkaloid which induces Ca2+ leakage from the SR, abolished postextrasystole potentiation; however, in the presence of ryanodine the extrasystole was potentiated. Caffeine, a phosphodiesterase inhibitor which induces SR Ca2+ release and impairs uptake, also abolished postextrasystole potentiation. As with ryanodine there was resultant potentiation of the extrasystole. In the case of caffeine the calcium transient consisted of a second slow component associated with extrasystole twitch potentiation. The results are consistent with sarcolemmal Ca2+ influx playing a role in potentiation of the extrasystole in the presence of an impaired SR. These data indicate that transsarcolemmal Ca2+ influx in the presence of impaired intracellular Ca2+ buffering can directly activate the myofilaments in agreement with reports on human myocardium.
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PMID:Cellular mechanisms of paired electrical stimulation in ferret ventricular myocardium: relationship between myocardial force and stimulus interval change. 140 34

Caffeine effects on contractile and acetylcholine receptor-related non-contractile Ca2+ mobilization were investigated in phrenic nerve-diaphragm muscles of mice with neostigmine. Caffeine enhanced at 0.25-5 mM, and decreased at 7-20 mM the total amount of contractile Ca(2+)-aequorin luminescence (Ca2+ transients), but only decreased at 2-10 mM non-contractile Ca2+ transients. Pretreatment with formamide (2 M for 30 min) abolished contractile Ca2+ transients, but did not affect non-contractile ones. These results suggest that non-contractile Ca2+ mobilization is not due to direct Ca2+ release from sarcoplasmic reticulum, but due to direct modulation by nicotinic acetylcholine receptor.
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PMID:Reversed effect of caffeine on non-contractile and contractile Ca2+ mobilization operated by acetylcholine receptor in mouse diaphragm muscle. 188 13

The effects of the methylxanthine, caffeine, on heat sensitization was investigated using Chinese hamster ovary (CHO) cells. Caffeine sensitized CHO cells to heat killing by reducing both the shoulder and the slope of the 44 degrees C survival curve. Heating was performed in suspension by addition of cells to preheated spinner flasks containing caffeine. Changes in intracellular free calcium levels, [Ca2+]i, were measured at 37 degrees C using the luminescent probe aequorin. Caffeine (1-5 mM) induced a transient increase in [Ca2+]i at 37 degrees C. The transient increase in [Ca2+]i was reduced 15-fold when 5 mM caffeine was added to aequorin-loaded cells suspended in Ca(2+)-free Hanks' balanced salt solution. However, 5 mM caffeine sensitized the cells to the same extent when they were suspended in either Ca(2+)-containing or Ca(2+)-free Hanks' balanced salt solution. The mechanism of heat sensitization by caffeine is still unknown.
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PMID:Caffeine sensitization of Chinese hamster ovary cells to heat killing. 188 80

Intracellular Ca2+ mobilization in neuro-skeletal muscle synapse was studied by measuring Ca2(+)-aequorin luminescence transients (Ca2+ transients). Ca2+ transients were categorized into three groups as follows: (1) The 1st phase of rapid Ca2+ mobilization was accompanied with twitch tension, (2) the 2nd phase of slow Ca2+ mobilization was not accompanied with twitch tension, and only observed in the presence of cholinesterase inhibitors, and (3) the 3rd phase was spontaneous Ca2+ mobilization which was rather related to contracture. The caffeine effects were composed of 1st phase-potentiation (cyclic AMP increase?), 2nd phase-inhibition (n-acetylcholine receptor (AChR) closely related), and the increase of 3rd phase (Ca2+ release from salcoplasmic reticulum). d-Tubocurarine showed much higher potency for the inhibition of the 2nd phase than for that of the 1st phase. These results suggest that the 1st phase Ca2+ transients are related to T-type n-AChR channel, whereas the 2nd phase Ca2+ transients are related to S-type n-AChR channel and its mediated signal transduction.
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PMID:[Intracellular calcium ion mobilization and nicotinic acetylcholine receptor-mediated signal transduction in neuro-skeletal muscle synapse]. 219 1

A novel approach was developed allowing the measurement of steady-state force and intracellular calcium concentration ([Ca2+]i) in tetanized human ventricular trabeculae carneae without pharmacological intervention. We compared and contrasted three methods of assessing calcium sensitivity of the myofilaments: 1) force-[Ca2+] relations in skinned fiber preparations, 2) peak twitch force-peak [Ca2+]i relations, and 3) steady-state force-[Ca2+]i relations in intact muscles. Steady-state contractile activation was achieved rapidly by tetanizing intact human trabeculae, loaded with aequorin, a Ca2(+)-sensitive bioluminescent protein, at a stimulation frequency of 15-20 Hz. Steady-state force and [Ca2+]i were measured during tetani, and the force versus [Ca2+]i relation was obtained by varying the extracellular calcium concentration ([Ca2+]o). Force-[Ca2+]i relations obtained from control and myopathic hearts were fitted to the Hill equation: %Force = [Ca2+]inh/([Ca2+]inh50% + [Ca2+]inh), where nh is the Hill coefficient, and [Ca2+]50% is the [Ca2+] required for 50% activation. The curves of tetani had Hill coefficients of 5.21 +/- 0.20 (n = 6) and 5.61 +/- 0.60 (n = 10) and [Ca2+]50% of 0.56 +/- 0.05 microM (n = 6) and 0.54 +/- 0.09 microM (n = 10) in control and myopathic muscles, respectively. We also constructed peak force-peak [Ca2+]i relations using isometric twitches from the same muscles. These curves were shifted toward higher [Ca2+]i compared with the steady-state force-[Ca2+]i curve derived from tetani. Ryanodine (1 microM), which increased the time course of the Ca2+ and force transients, shifted the peak force-peak [Ca2+]i relation to the left, without affecting the steady-state force-[Ca2+]i relation. Exposure to 10 mM caffeine shifted the steady-state force-[Ca2+]i relation to the left, whereas exposure to 3 microM isoproterenol shifted this relation to the right. Experiments using skinned fiber preparations were performed in parallel with experiments on intact muscles from the same hearts. The force-pCa (-log[Ca2+]) relations in saponin-skinned trabeculae from control and myopathic tissue were superimposable. Ryanodine (1 microM) had no effect on the force-pCa relation in skinned fibers. Maximal tension was evoked by the posttetanic twitch, which was larger than the tetanus. This potentiation was abolished in the presence of ryanodine, a sarcoplasmic reticulum inhibitor. We propose that the changes in the steady-state force-[Ca2+]i relations are correlated with alterations in the sensitivity of the myofilaments to Ca2+, whereas changes in the peak force-peak [Ca2+]i relations represent temporal changes in the twitch transient.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Relation between steady-state force and intracellular [Ca2+] in intact human myocardium. Index of myofibrillar responsiveness to Ca2+. 220 17

Alternans in heart is important as pulsus alternans in cardiac failure and electrophysiological alternans in myocardial ischemia. The explanation of this phenomenon is still unclear. We attempted to investigate the cellular mechanisms of alternans by measuring intracellular free calcium concentration [( Ca2+]i) with the photoprotein aequorin in isolated ferret papillary muscles. Tension and length were also recorded simultaneously. Transient mechanical alternans lasting five to 20 contractions could be reliably induced in this preparation by following a 30-second rest period with stimulation at a fast rate (2-4 Hz). Production of sustained mechanical alternans, which lasted longer than 20 contractions and could persist for several hundred contractions, required additional interventions, consisting of a lower temperature (25 degrees C), a lower external calcium concentration (1 mM), and a lower pH (6.91) than control conditions (0.33-0.5 Hz, 30 degrees C, 2 mM Ca2+, pH 7.36). Transient mechanical alternans was associated with transient in-phase alternation of aequorin light and, hence, [Ca2+]i. Sustained mechanical alternans was associated with sustained in-phase alternation of aequorin light as well as incomplete relaxation of tension. However, when muscles were switched from isometric to unloaded isotonic contraction, relaxation between stimuli was complete but contraction and the aequorin light signal continued to alternate. The addition of 10 mM caffeine or 10 microns ryanodine abolished transient and sustained mechanical alternans and also abolished the associated alternation of aequorin light. Commensurate with the action of ryanodine, which allows the sarcoplasmic reticulum to reaccumulate calcium to a limited extent after a period of rapid stimulation, sustained mechanical alternans sometimes reappeared in an attenuated form 30 to 50 contractions after the addition of ryanodine. These results demonstrate that incomplete muscle relaxation between beats need not be present for alternans to occur, and support the hypothesis that alternans is caused by intracellular calcium cycling involving the sarcoplasmic reticulum.
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PMID:Changes in intracellular calcium during mechanical alternans in isolated ferret ventricular muscle. 230

Changes in intracellular Ca2+ release in the diaphragm muscle of alloxan-diabetic mice were compared with changes in normal muscles and non-diabetic denervated muscles. We measured Ca2+ transient aequorin luminescence by direct electrical stimulation of these muscles. External Ca2(+)-free solution readily decreased the Ca2+ transient in normal muscles but had less of an effect in diabetic muscles. Only when the muscles were pre-injected with EGTA (reducing intracellular levels of free Ca2+) did the Ca2+ transients decrease significantly in diabetic muscles, however, there was no effect in denervated muscles. The caffeine-induced increase in Ca2+ transients, however, was delayed in both diabetic muscles and non-diabetic denervated muscles. The caffeine response was observed in normal muscles under the external Ca2(+)-free conditions even after EGTA-pretreatment, whereas it was suppressed, after a brief increase, in both diabetic and non-diabetic denervated muscles. These results demonstrate (1) the insensitivity of intracellular Ca2+ mobilization to external Ca2+ levels and the ready accumulation of intracellular Ca2+ in the cytosol in the diabetic state, (2) increased permeability to Ca2+ in the denervated state and (3) impairment of the Ca2+ pool which responds to caffeine in both diabetes and the non-diabetic denervated state. Diabetic neuromyopathy thus appears to be a state of abnormal Ca2(+)-mobilization caused secondarily by high levels of blood glucose.
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PMID:Increase in electrically-stimulated Ca2+ release and suppression of caffeine response in diaphragm muscle of alloxan-diabetic mice compared with the denervation effect. 232 47

Addition of norepinephrine, angiotensin II, or histamine leads to a transient rise in the cytoplasmic Ca2+ concentration ([Ca2+]i), as measured with aequorin, in rabbit aortic strips. Each induces a [Ca2+]i transient which peaks in 2 min and then falls either back to baseline (angiotensin II) or to a plateau (norepinephrine and histamine). The [Ca2+]i transient is due to the mobilization of Ca2+ from a caffeine-sensitive, intracellular pool. An elevation of [K+] to 35 mM leads to a monotonic sustained rise in [Ca2+]i which depends entirely on extracellular Ca2+, but an increase to 100 mM leads to a [Ca2+]i transient from the mobilization of intracellular Ca2+. Atrial natriuretic peptide does not alter basal [Ca2+]i nor inhibit the [Ca2+]i transient induced by either histamine or angiotensin II, but blocks that induced by norepinephrine, and blocks the plateau phase induced by either histamine or norepinephrine. The peptide inhibits the contractile response to all three agonists and to K+.
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PMID:Measurement of cytoplasmic free Ca2+ concentration in rabbit aorta using the photoprotein, aequorin. Effect of atrial natriuretic peptide on agonist-induced Ca2+ signal generation. 243 45

1. Single muscle fibres were dissected from Xenopus lumbrical muscles and microinjected with the photoprotein aequorin in order to measure the myoplasmic free calcium concentration ([Ca2+]i). Fatigue was produced by repeated intermittent tetanic stimulation continued until tension had declined to approximately 50% of the initial level. Fibres were then allowed to recover by giving tetani at less frequent intervals. Aequorin light (a measure of [Ca2+]i) and tension were measured during fatiguing stimulation and recovery. 2. During fatiguing stimulation, tetanic tension declined steadily, but peak aequorin light first increased before declining substantially. The largest light signal was about 155% of initial control while at the end of fatiguing stimulation the tetanic light fell to about 14% of control. 3. Fibres showed a characteristic slowing of relaxation in the fatigued state. This was associated with a slowing of the rate of decline of the aequorin light signal. 4. Intracellular acidosis produced by equilibrating the Ringer solution with either 5 or 15% CO2 caused an increase in the light signal associated with a tetanus. Carbon dioxide also caused a reduction of tension and a slowing of relaxation. 5. In vivo pCa-tension curves were constructed by exposing the fibres to a series of K+ concentrations which produced contractures of different sizes. Light and tension were measured during periods when both were relatively stable and the light signal was subsequently converted to pCa. 6. Exposure of fibres to 5 or 15% CO2 caused the pCa-tension curve to be shifted to the right of the control curve. This indicates a reduced Ca2+ sensitivity of the contractile proteins, which is in agreement with results from skinned fibre studies. 7. The pCa-tension points obtained from tetani during the early part of fatiguing stimulation also deviated to the right of the control pCa-tension curve, suggesting a reduced Ca2+ sensitivity of the contractile proteins. At the end of fatiguing stimulation, however, pCa-tension points did not differ greatly from the control pCa-tension curve, suggesting that Ca2+ sensitivity was approximately normal. Thus the reduced [Ca2+]i during tetani at the end of fatiguing stimulation (when tension was reduced to approximately 50%) could explain all of the reduction in tension. 8. After fatiguing stimulation, tension and light recovered monotonically in some fibres; however, in the majority of fibres, tension and light showed a secondary decline followed by a slower recovery (post-contractile depression). 9. During post-contractile depression, caffeine contractures or tetani in the presence of caffeine gave increased aequorin light signals and the tension developed was close to that produced in an unfatigued tetanus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Intracellular calcium and tension during fatigue in isolated single muscle fibres from Xenopus laevis. 251 88


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