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At least 181 records · Page 10Linked to original sources
PubMed1984

Excitation-contraction coupling in cardiac Purkinje fibers. Effects of cardiotonic steroids on the intracellular [Ca2+] transient, membrane potential, and contraction.

The [Ca2+]-activated photoprotein aequorin was used to measure [Ca2+] in canine cardiac Purkinje fibers during the positive inotropic and toxic effects of ouabain, strophanthidin, and acetylstrophanthidin. The positive inotropic effect of these substances was associated with increases in the two components of the aequorin signal, L1 and L2. On the average, strophanthidin at 10(-7) M produced steady, reversible increases in L1, L2, and peak twitch tension of 20, 91, and 240%, respectively. This corresponds to increases in the upper-limit spatial average [Ca2+] from 1.9 X 10(-6) M to 2.1 X 10(-6) M at L1 and from 1.4 X 10(-6) M to 1.8 X 10(-6) M at L2. Elevation of diastolic luminescence above the control level was not detected. At higher concentrations (5 X 10(-7) M), strophanthidin produced aftercontractions, diastolic depolarization, and transient depolarizations, all of which were associated with temporally similar changes in [Ca2+]. During these events, diastolic [Ca2+] rose from the normal level of approximately 3 X 10(-7) M up to 1-2 X 10(-6) M. The negative inotropic effect of 5 X 10(-7) M strophanthidin was not associated with a corresponding decrease in the [Ca2+] transient but was associated with a change in the relationship between [Ca2+] and tension. Assuming the Na+-lag mechanism of cardiotonic steroid action, we conclude the following: at low concentrations of drug, increased Ca2+ uptake by the sarcoplasmic reticulum prevents a detectable rise in cytoplasmic [Ca2+] during diastole, but this increased Ca2+ uptake results in increased release of Ca2+ during the action potential. At higher drug concentrations, observable [Ca2+] changes during diastole activate tension and membrane conductance changes.

Action Potentials↗
PubMed1984

Excitation-contraction coupling in cardiac Purkinje fibers. Effects of caffeine on the intracellular [Ca2+] transient, membrane currents, and contraction.

The effects of caffeine on tension, membrane potential, membrane currents, and intracellular [Ca2+], measured as the light emitted by the Ca2+-activated photoprotein aequorin, were studied in canine cardiac Purkinje fibers. An initial, transient, positive inotropic effect of caffeine was accompanied by a transient increase in the second component of the aequorin signal (L2) but not the first (L1). In the steady state, 4 or 10 mM caffeine always decreased twitch tension and greatly reduced both L1 and L2. At a concentration of 2 mM, caffeine usually reduced but occasionally increased the steady state twitch tension. However, 2 mM caffeine always reduced both L1 and L2. Caffeine eliminated the diastolic oscillations of intracellular [Ca2+] induced by high extracellular [Ca2+]. In voltage-clamp experiments, 10 mM caffeine reduced the transient outward current and the peak tension elicited by step depolarization from a holding potential of -45 mV. In the presence of 20 mM Cs+, 10 mM caffeine reduced slow inward current. However, the time course of this reduction was far slower than that in tension and light observed in separate experiments. The simplest explanation of the results is that caffeine inhibits the sequestration of Ca2+ by the sarcoplasmic reticulum. The results also suggest that in Purkinje fibers caffeine increases the sensitivity of the myofilaments to Ca2+.

Action Potentials↗
PubMed1979

Excitation-contraction coupling in normal and myopathic hamster hearts I: identification of a calcium pool involved in contraction.

The results of this study indicate that two min of Ca-free perfusion did not significantly alter the exchange kinetics of mannitol or Ca in isolated heart preparations. A numerical solution for series Ca exchange between a superficial Ca pool, Ca1, and an intracellular pool, Ca2, was developed in terms of the coefficients and constants determined from a parallel analysis. The series and parallel models for Ca efflux yielded a high correlation between contractile activity and the rate of exchange and Ca content of Ca1. The kinetics of Ca influx were best described by a series model of exchange and agreed closely with the Ca contents and exchange properties measured during Ca efflux. No differences were detected between normal and myopathic hamster hearts in the kinetics of Ca exchange or the role of Ca1 in the E-C coupling process.

Animals↗
PubMed2003

Medicare contracting risk/Medicare risk contracting: a life-cycle view from twelve markets.

OBJECTIVE: To examine the evolution of the Medicare HMO program from 1996 to 2001 in 12 nationally representative urban markets by exploring how the separate and confluent influences of government policy initiatives and health plans' strategic aims and operational experience affected the availability of HMOs to Medicare beneficiaries. DATA SOURCE: Qualitative data gathered from 12 nationally representative urban communities with more than 200,000 residents each, in tandem with quantitative information from the Centers for Medicare and Medicaid Services and other sources. STUDY DESIGN: Detailed interview protocols, developed as part of the multiyear, multimethod Community Tracking Study of the Center for Studying Health System Change, were used to conduct three rounds of interviews (1996, 1998, and 2000-2001) with health plans and providers in 12 nationally representative urban communities. A special focus during the third round of interviews was on gathering information related to Medicare HMOs' experience in the previous four years. This information was used to build on previous research to develop a longitudinal perspective on health plans' experience in Medicare's HMO program. PRINCIPAL FINDINGS: From 1996 to 2001, the activities and expectations of health plans in local markets underwent a rapid and dramatic transition from enthusiasm for the Medicare HMO product, to abrupt reconsideration of interest corresponding to changes in the Balanced Budget Act of 1997, on to significant retrenchment and disillusionment. Policy developments were important in their own right, but they also interacted with shifts in the strategic aims and operational experiences of health plans that reflect responses to insurance underwriting cycle pressures and pushback from providers. CONCLUSION: The Medicare HMO program went through a substantial reversal of fortune during the study period, raising doubts about whether its downward course can be altered. Market-level analysis reveals that virtually all momentum for the program has been lost and that enrollment is shrinking back to the levels and locations found in the mid-1990s.

Contract Services↗
PubMed1990

Effects of pre-contraction with endothelin-1 on alpha 2-adrenoceptor- and (endothelium-dependent) neuropeptide Y-mediated contractions in the isolated vascular bed of the rat tail.

1. The pressor effects to bolus doses of the alpha 2-adrenoceptor agonist UK-14,304 were studied in the isolated vascular bed of the perfused rat tail before and after increasing the perfusion pressure with infusions of endothelin-1. Those of neuropeptide Y were studied before and after pre-constriction with endothelin-1 or 5-hydroxytryptamine. The pressor effects of neuropeptide Y were studied before and after functional disruption of the endothelium with the detergent CHAPS. 2. Endothelin-1 and the alpha 1-adrenoceptor agonist phenylephrine induced dose-dependent vasoconstriction, endothelin-1 being some 10(4) times more potent than phenylephrine [log dose (mol) of the ED50 for endothelin-1 and phenylephrine: -11.8 +/- 0.2 (n = 7), -8.2 +/- 0.2 (n = 5) respectively]. 3. Under control conditions, at basal perfusion pressures, UK-14,304 and neuropeptide Y were virtually inactive as vasoconstrictors. Following a sustained increase in perfusion pressure by infusions of endothelin-1 (2.5-10 nM at 0.8 ml min-1), however, both UK-14,304 and neuropeptide Y induced dose-dependent pressor responses and both were some 10(2) times more potent than phenylephrine [log dose (mol) of the ED50 for UK-14304 and neuropeptide Y: -10 +/- 0.5 (n = 6), -10.3 +/- 0.4 (n = 6) respectively]. Responses to neuropeptide Y also were uncovered when vascular tone was increased with 5-hydroxytryptamine (5-20 nM) [log dose (mol) of the ED50 for neuropeptide Y: -10.2 +/- 0.2 (n = 6)]. 4. Pre-constriction-induced pressor responses to UK-14,304 were inhibited by 1 microM rauwolscine whilst those to neuropeptide Y were inhibited by disruption of the endothelium. Removal of the endothelium had no significant effect on the pressor responses to 4pmol or 8pmol endothelin-1 and had no effect on the increase in perfusion pressure induced by the endothelin-1 infusions but did decrease the time-course of pressor responses to bolus injections of endothelin-1. Endothelial disruption had no significant effect on the vasoconstriction induced by all but one of the doses of phenylephrine administered [log dose (mol) of the ED5o for phenylephrine after CHAPS: -8.6 + 0.2 (n = 5)], indicating that the responsiveness of the vascular smooth muscle was not destroyed by CHAPS. This treatment did, however, slow the onset and prolong the time course of the phenylephrine-induced responses. 5. These results indicate that, in the isolated vascular bed of the rat tail, pressor responses to both alpha 2-adrenoceptor- and neuropeptide Y receptor-activation are uncovered by agonist-induced preconstriction including that to endothelin-1. Neuropeptide Y-induced vasoconstriction was endotheliumdependent.

Animals↗
PubMed1991

Role of Ca2+ channel in cardiac excitation-contraction coupling in the rat: evidence from Ca2+ transients and contraction.

1. Optical methods were used to measure simultaneously unloaded cell shortening and intracellular Ca2+ transients in whole-cell voltage clamped rat ventricular myocytes. Red light (greater than 670 nm) was used to measure cell shortening with a linear photodiode array. The dyes Fura-2 (Kd = 140 nM) and Mag-Fura-2 (Kd = 44 microM) were used as Ca2+ indicators with fluorescence excitation at 340 and 410 nm and emission at 510 nm. 2. Repeated measurements at 6 s intervals as 0.4 mM-Fura-2 diffused into the cell from the tip of the voltage clamp pipette showed no decrease in the rate of rise and peak value of the intracellular Ca2+ transient and only a small suppression of cell shortening, suggesting that the molecular mechanisms regulating the Ca2+ release were not significantly altered by the buffering capacity of the Fura-2. 3. Experiments in which the sarcoplasmic reticulum (SR) was depleted of Ca2+ either by exposure to caffeine or by repeated brief (20 ms) voltage clamp depolarizations confirm that the SR is the major source of activator Ca2+. 4. Mag-Fura-2 (1 or 5 mM) was used to register the initial rapid development of the [Ca2+]i transient but the later time course of the Ca2+ transients measured with this dye was obscured by motion artifacts resulting from cell shortening. 5. Both Fura-2 and Mag-Fura-2 showed that depolarization to 0 mV from a holding potential of -80 mV resulted in a [Ca2+]i transient which developed with a delay of 3-9 ms and approached its peak value in an additional 8-19 ms. Both Ca2+ indicators also showed that the Ca2+ transient approached its peak value more slowly as the clamped membrane potential was made increasingly more positive. 6. The voltage dependencies of the Ca2+ signal (Fura-2) and cell shortening were both bell-shaped and were qualitatively similar to the voltage dependence of Ca2+ current simultaneously measured. This was observed with holding potentials of both -40 and -80 mV. 7. Comparison of the temporal relation of the Ca2+ current, ICa, and intracellular Ca2+ transient (Fura-2) and cell shortening at different membrane potentials showed that Ca2+ transient measured 25 ms into the depolarization correlated closely to the integral of the Ca2+ current measured prior to this time. Cell shortening, on the other hand, peaked about 100 ms later and correlated with measurements of the Ca2+ activity at the later time.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗