Biomedical subjects

J Y Cheung

Publications and source records attributed to J Y Cheung.

At least 37 records · Page 2Linked to original sources

PubMed1998

Diagnosis and radioablation treatment of toxic multinodular goiter in a hemodialysis patient.

Toxic multinodular goiter is rare in hemodialysis patients. In addition, establishing the diagnosis of hyperthyroidism in the elderly patient with renal failure is difficult because abnormal thyroid function tests can erroneously be attributed to euthyroid sick syndrome. Treatment of hyperthyroidism in dialysis patients by radioiodine ablation involves careful calculation of 131I dose, determination of interval between 131I administration and its removal by hemodialysis, and minimization of radiation hazards during dialytic removal of 131I. We described the clinical presentation of an elderly dialysis patient with toxic multinodular goiter and discussed our diagnostic and therapeutic approaches. The patient's recovery after 131I ablation was complete and uneventful.

Aged↗

PubMed1998

Endurance exercise alters the contractile responsiveness of rat heart to extracellular Na+ and Ca2+.

PURPOSE AND METHODS: The isovolumic contractile responsiveness of left ventricular (LV) myocardium to altered extracellular [Ca2+], [Na+], and pacing frequency was examined using perfused hearts (37 degrees C) isolated from sedentary (SED) and treadmill-trained (TR) adult female rats. RESULTS: The suppressive effect of reducing perfusate free [Ca2+] to 0.7 mM on LV developed pressure (delta LVP) was greater in the TR hearts compared with SED hearts (P < 0.05). When perfusate [Na+] was reduced to 120 mM ([Ca2+] = 0.7 mM), delta LVP augmentation was greatest in the TR hearts (P < 0.05). The negative force-frequency relationship observed at physiologic [Ca2+] and [Na+] was progressively altered toward a positive force-frequency relationship with each subsequent change in perfusate [Ca2+] and [Na+] although the effect was greatest in TR hearts (P < 0.05). CONCLUSIONS: Training elicited a small but significant (P < 0.05) prolongation in the pressure development phase of contraction. Under the physiological [Ca2+], [Na+] perfusion condition, training produced an increase in the magnitude of extrasystolic potentiation of LV pressure, whereas the time constant of mechanical restitution was unaffected. Training affected neither the Ca(2+)-dependence nor the maximal capacity of [3H] ryanodine binding to LV myocardial homogenates. The simplest interpretation of [Na+] and [Ca2+] reduction experiments is that myocardial Ca2+ efflux was augmented by exercise training.

Adaptation, Physiological↗

PubMed1998

Monte Carlo calculation of single-beam dose profiles used in a gamma knife treatment planning system.

The accuracy of single-beam dose profiles used in the algorithm of the Gamma Knife treatment planning system (Leksell GammaPlan) is verified. EGS4 Monte Carlo calculation was employed to calculate the dose distributions of single-beams in a spherical water phantom with diameter 160 mm. The beams were directed to the center of the phantom. Collimators of 4, 8, 14, and 18 mm sizes were studied. The single-beam dose profiles provided by Elekta (Manufacturer of Leksell Gamma Knife) were excellently consistent with the results of Monte Carlo for the 4, 14, and 18 mm collimators. The maximum discrepancy was less than 3% at all radial distances. For the 8 mm collimator, the maximum discrepancy was 8% in the relative dose in the radial distance range from 4.3 mm to 5.2 mm. Excellent agreement in dose profiles along x, y, and z axes for all collimator helmets by summing over all 201 sources was observed between the cases using the default single-beam dose profiles and the calculated Monte Carlo results, except for the 8 mm collimator helmet along z axis. Such difference may however be too small to give a clinical significance.

Algorithms↗

PubMed1998

Response of isolated rat descending vasa recta to bradykinin.

Outer medullary descending vasa recta (OMDVR) were dissected from the outer medullary vascular bundles of young rats, perfused in vitro, and loaded with fura 2 for measurement of intracellular calcium concentration ([Ca2+]i) by fluorescent ratio imaging. Fluorescent video images revealed that fura 2 selectively loads into endothelial cells but not pericytes. Bradykinin (BK), at concentrations > 10(-11) M, elicited an increase in [Ca2+]i from baseline values in the range from 50 to 100 nM to peak values of 600-800 nM followed by a sustained plateau of 150-250 nM. The vasopressin V1-receptor agonist [Phe2,Ile3,Orn8]vasopressin constricted OMDVR but yielded no observable [Ca2+]i response, a finding that is consistent with an endothelial cell origin for the fura 2 fluorescent signal. The BK [Ca2+]i response was blocked by the selective BK B2-receptor antagonists D-Arg-[Hyp3,Thi5.8,D-Phe7]BK and D-Arg-[Hyp3,D-Phe7,Leu8]BK but not the B1 antagonist des-Arg9-[Leu8]BK. BK vasodilated microperfused OMDVR that had been preconstricted with 10(-8) M angiotensin II. We conclude that the [Ca2+]i response of OMDVR endothelia can be selectively studied with fura 2, that BK increases endothelial [Ca2+]i via the B2 receptor, and that BK can vasodilate descending vasa recta.

Angiotensin II↗

PubMed1998

Sprint training attenuates myocyte hypertrophy and improves Ca2+ homeostasis in postinfarction myocytes.

Myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) had decreased Na+/Ca2+ exchange currents (I Na/Ca; 3 Na+ out:1 Ca2+ in) and sarcoplasmic reticulum (SR)-releasable Ca2+ contents. These defects in Ca2+ regulation may contribute to abnormal contractility in MI myocytes. Because exercise training elicits positive adaptations in cardiac contractile function and myocardial Ca2+ regulation, the present study examined whether 6-8 wk of high-intensity sprint training (HIST) would ameliorate some of the cellular maladaptations observed in post-MI rats with limited exercise activity (Sed). In MI rats, HIST did not affect citrate synthase activities of plantaris muscles but significantly increased the percentage of cardiac alpha-myosin heavy chain (MHC) isoforms (57.2 +/- 1.9 vs. 49.3 +/- 3.5 in MI-HIST vs. MI-Sed, respectively; P < or = 0.05). At the single myocyte level, HIST attenuated cellular hypertrophy observed post-MI, as evidenced by reductions in cell lengths (112 +/- 4 vs. 130 +/- 5 micrograms in MI-HIST vs. MI-Sed, respectively; P < or = 0.005) and cell capacitances (212 +/- 8 vs. 242 +/- 9 pF in MI-HIST vs. MI-Sed, respectively; P < or = 0.015). Reverse I Na/Ca was significantly lower (P < or = 0.0001) in myocytes from MI-Sed rats compared with those from rats that were sham operated and sedentary. HIST significantly increased reverse I Na/Ca (P < or = 0.05) without affecting the amount of Na+/Ca2+ exchangers (detected by immunoblotting) in MI myocytes. SR-releasable Ca2+ content, as estimated by integrating forward I Na/Ca during caffeine-induced SR Ca2+ release, was also significantly increased (P < or = 0.02) by HIST in MI myocytes. We conclude that the enhanced cardiac output and stroke volume in post-MI rats subjected to HIST are mediated, at least in part, by reversal of cellular maladaptations post-MI.

Animals↗

PubMed1998

'Tweaked' GammaPlan for target volume measurement in non-fiducial based images: a simple routine for follow-up assessment.

The GammaPlan provides accurate estimation of target volume. However, a stereotactic frame and fiducials are required. At follow-up MR/CT, fiducials are no longer available. Surgeons rely on visual impression, 2-D measurements, or other methods to estimate the volume of the treated targets. These methods are not objective and may give rise to misleading conclusions. By modifying the image header files of GammaPlan version 3, it is possible to scale the images which are not acquired with stereotactic fiducials. The target is then mapped and its volume measured as usual. The target volumes in 7 patients were measured by the tweaked GammaPlan and compared with volume measurements using the standard version. The mean error was less than 2%. In a separate study, phantom syringes with known volumes of water were used for MR imaging. The tweaked version again gave accurate volume estimation of the phantom syringes with a less than 5% error for most cases. This method has subsequently been used in all Gamma Knife follow-up cases. Significant volume changes have been detected where conventional assessment showed no apparent change. Moreover, such volume changes correlated with clinical improvement or deterioration. It is recommended that all Gamma Knife users report tumor response by volume change. Our method is simple, reliable and does not require additional cost.

Follow-Up Studies↗

PubMed1997

Modulation of calcium channels in human erythroblasts by erythropoietin.

Erythropoietin (Epo) induces a dose-dependent increase in intracellular free Ca2+ ([Ca2+]i) in human erythroblasts, which is dependent on extracellular Ca2+ and blocked by high doses of nifedipine or Ni2+. In addition, pretreatment of human erythroblasts with mouse antihuman erythropoietin receptor antibody but not mouse immunopure IgG blocked the Epo-induced [Ca2+]i increase, indicating the specificity of the Ca2+ response to Epo stimulation. In this study, the erythropoietin-regulated calcium channel was identified by single channel recordings. Use of conventional whole cell patch-clamp failed to detect Epo-induced whole cell Ca2+ current. To minimize washout of cytosolic constituents, we next used nystatin perforated patch, but did not find any Epo-induced whole cell Ca2+ current. Using Ba2+ (30 mmol/L) as charge carrier in cell-attached patches, we detected single channels with unitary conductance of 3.2 pS, reversal potential of +72 mV, and whose unitary current (at +10 mV) increased monotonically with increasing Ba2+ concentrations. Channel open probability did not appreciably change over the voltage range (-50 to +30 mV) tested. Epo (2 U/mL) increased both mean open time (from 4.27 +/- 0.75 to 11.15 +/- 1.80 ms) and open probability (from 0.26 +/- 0.06 to 2.56 +/- 0.59%) of this Ba(2+)-permeable channel. Our data strongly support the conclusion that the Epo-induced [Ca2+]i increase in human erythroblasts is mediated via Ca2+ entry through a voltage-independent Ca2+ channel.

Animals↗

PubMed1997

Hypertension alters rapid cooling contractures in single rat cardiocytes.

Previous work has demonstrated that, in single, paced left ventricular (LV) myocytes isolated from rats with hypertension, the extent of myocyte shortening and the amplitude of the cytosolic Ca2+ concentration transient are decreased relative to normal myocytes. These findings suggest that reduced sarcoplasmic reticular (SR) Ca2+ release could be responsible for hypertension-induced attenuation of the myocyte contractile response. Hypertension-induced reductions in SR Ca2+ release could be due to 1) a decrease in releasable SR Ca2+ content relative to the sarcoplasmic volume into which it is released or 2) alterations in the SR Ca2+ release mechanism such that the fractional release of SR Ca2+ is reduced. Using rapid cooling contractures (RCCs) to provide an index of SR Ca2+ content, we conducted a series of experiments designed to test the former hypothesis. Single LV myocytes were isolated from normotensive control rats and from rats with hypertension, which was induced by abdominal aortic banding (for approximately 4 mo). The extent of myocyte shortening during an RCC is taken to be directly proportional to SR Ca2+ content. As expected, the amplitudes of both twitches and RCCs decreased as pacing frequency increased from 0.2 to 1.0 Hz across both control and hypertensive groups, although the effect was greatest in control myocytes. A significant finding of this study was that, at both pacing frequencies, RCC magnitude was attenuated in hypertensive relative to control myocytes. These results suggest that in hypertension cellular Ca2+ homeostasis is altered and there is a mismatch between releasable SR Ca2+ content and the sarcoplasmic volume into which it is released.

Animals↗

PubMed1997

Endurance training does not affect intrinsic calcium current characteristics in rat myocardium.

The voltage-dependent Ca2+ channel (L-type channel) controls an inward Ca2+ current (ICa) that is centrally involved in the regulation of myocardial excitation-contraction (EC) coupling. A significant body of evidence exists to support the idea that exercise training elicits alterations in myocardial Ca2+ regulation, and the L-type channel has been implicated as a possible site of adaptation. The purpose of this study was to determine whether training elicits adaptations at the level of the L-type Ca2+ channel, as reflected by alterations in whole cell ICa characteristics in single myocytes isolated from rat left ventricle (LV). Female rats were treadmill trained at a moderately high intensity for a minimum of 20 wk. Body weight was unaffected by the training protocol, whereas there was a trend (P = 0.06) for a modest increase in LV weight (approximately 8%). Training produced significant (P < 0.05) increases in mean myocyte capacitance (approximately 9%) and myocyte length (approximately 6%), thus providing electrophysiological and morphological evidence that training elicited LV cardiocyte hypertrophy. Whole cell ICa vs. voltage and ICa density vs. voltage relationships as well as ICa inactivation and recovery characteristics were unaffected by our training paradigm. These findings do not support the hypothesis that training elicits adaptations in L-type Ca2+ channel number or intrinsic function in a model exhibiting classical exercise training-induced myocardial hypertrophy. Our results do not, however, preclude the possibility that training-induced adaptations at sites other than the L-type Ca2+ channel could affect ICa and myocardial EC coupling.

Animals↗

PubMed1996

G-protein alpha subunit Gi(alpha)2 mediates erythropoietin signal transduction in human erythroid precursors.

Erythropoietin induces a dose-dependent increase in cytosolic calcium in human erythroblasts that is mediated by a voltage-independent Ca2+ channel. Inhibition of this response to erythropoietin by pertussis toxin suggests involvement of guanine nucleotide-binding regulatory proteins (G-proteins). The role of G-proteins in regulation of the erythropoietin-modulated Ca2+ channel was delineated here by microinjection of G-protein modulators or subunits into human erythroid precursors. This is the first report on the use of microinjection to study erythropoietin signal transduction in normal precursor cells. Fura-2 loaded day-10 burst-forming units-erythroid-derived erythroblasts were used for microinjection and free intracellular calcium concentration ([Ca(i)]) was measured with digital video imaging. BCECF (1,2',7'-bis(2-carboxyethyl)-5-(and -6-)-carboxyfluorescein) was included in microinjectate, and an increase in BCECF fluorescence was evidence of successful microinjection. Cells were microinjected with nonhydrolyzable analogues of GTP, GTPgammaS or GDPbetaS, which maintain the alpha subunit in an activated or inactivated state, respectively. [Ca(i)] increased significantly in a dose-dependent manner after microinjection of GTPgammaS. However, injection of GDPbetaS blocked the erythropoietin-induced calcium increase, providing direct evidence that activation of a G-protein is required. To delineate which G-protein subunits are involved, alpha or betagamma transducin subunits were purified and microinjected as a sink for betagamma or alpha subunits in the erythroblast, respectively. Transducin betagamma, but not alpha, subunits eliminated the calcium response to erythropoietin, demonstrating the primary role of the alpha subunit. Microinjected antibodies to Gi(alpha)2, but not Gi(alpha)1 or Gi(alpha)3, blocked the erythropoietin-stimulated [Ca(i)] rise, identifying Gi(alpha)2 as the subunit involved. This was confirmed by the ability of microinjected recombinant myristoylated Gi(alpha)2, but not Gi(alpha)1 or Gi(alpha)3 subunits, to reconstitute the response of pertussis toxin-treated erythroblasts to erythropoietin. These data directly demonstrate a physiologic function of G-proteins in hematopoietic cells and show that Gi(alpha)2 is required in erythropoietin modulation of [Ca(i)] via influx through calcium channels.

Calcium↗

PubMed1996

A radiological approach to the through and through technique for percutaneous passage of ureteric strictures.

Some ureteric strictures are so tight that they are difficult to traverse with balloon catheters or internal stents. We present five such cases, which were traversed using a modified through and through technique with a hydrophilic coated guide-wire. The reasons for the difficulty are discussed, and the merits of the modified technique compared with conventional techniques are described.

Catheterization↗

PubMed1996

Quantitative assessment of the variation within grades of facial paralysis.

A completely objective, unambiguous outcome measure of facial function is now available. A new automated computer-assisted clinimetric system combines the crucial detection capabilities of the human observer and the unique capacity of the computer to quantify the image light reflectance difference observed during facial expression. The new system was applied to 27 patients with a variety of diseases affecting the facial nerve. All subjects could be individually and objectively ranked, and disease-specific profiles could be constructed. These tasks are not possible with the House-Brackmann scale, because of the wide variation within grades and the ambiguity between grades. With the automated objective, unambiguous outcome measure, it may be possible to define individual case progression, recovery, and outcome over the course of disease.

Cranial Nerve Neoplasms↗

PubMed1996

Na+/Ca2+ exchange currents and SR Ca2+ contents in postinfarction myocytes.

Myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) had lower peak cytosolic free Ca2+ concentration ([Ca2+]i) and reduced maximal extent of cell shortening during contraction, but Ca2+ entry via L-type Ca2+ channels was normal. In the current study using whole cell patch-clamp technique, reverse Na+/Ca2+ exchange current (INa/Ca; 3 Na+ out:1 Ca2+ in) was measured in myocytes in which Na+, K+, and Ca2+ currents were blocked or minimized. Steady-state outward currents measured under these conditions increased with depolarization or with elevation of extracellular Ca2+ concentration ([Ca2+]o) from 1.8 to 5.0 mM, but were inhibited by 5 mM Ni2+ or by reduction of [Ca2+]i to near zero. In addition, reduction of cytosolic free Na+ concentration or of [Ca2+]i also decreased the amplitude of the outward current. These characteristics indicate the outward current was INa/Ca operating in reverse mode. Reverse INa/Ca was significantly lower in MI myocytes, especially at more positive voltages. In addition, sarcoplasmic reticulum (SR)-releasable Ca2+ content as estimated by integrating forward INa/Ca during caffeine-induced SR Ca2+ release was also significantly lower in MI myocytes. Depressed Na+/Ca2+ exchange activity may contribute to abnormal [Ca2+]i dynamics in MI myocytes.

Animals↗

PubMed1996

Regulation of rDNA transcription during endothelin-1-induced hypertrophy of neonatal cardiomyocytes. Hyperphosphorylation of upstream binding factor, an rDNA transcription factor.

Treatment of cultured neonatal cardiomyocytes with endothelin-1 and phorbol 12-myristate 13-acetate (PMA) results in cardiomyocyte hypertrophy. However, the signal transduction pathways involved in this process are poorly understood. Because increased ribosome biogenesis is a requisite for hypertrophy, we sought to (1) confirm the hypothesis that these two hypertrophic agents did indeed induce rRNA synthesis and (2) examine the mechanism through which this induction was accomplished. In this study, hypertrophy of contraction-arrested neonatal cardiomyocytes induced by treatment with either endothelin-1 or PMA was associated with increased rDNA transcription. Western blots demonstrated that the enhanced rates of rDNA transcription were not mediated by increased amounts of either RNA polymerase I or upstream binding factor (UBF), an rDNA transcription factor. However, immunoprecipitation of [32P] orthophosphate-labeled UBF from hypertrophying neonatal cardiomyocytes suggested that the increased rate of rDNA transcription may be due to the hyperphosphorylation of UBF, which would increase the activity of UBF. The increase in UBF phosphorylation occurred within 3 to 6 hours after exposure to either agent, was maximal at 12 hours, and was sustained for at least the first 24 hours of exposure. Phosphoamino acid analysis of UBF immunoprecipitated from control and treated cardiomyocytes demonstrated that UBF was phosphorylated exclusively on serine residues. Our previous studies have shown that the cellular UBF content increased in adrenergic- and contraction-induced models of cardiac hypertrophy. This study with endothelin-1 and PMA demonstrates that the modulation of UBF phosphorylation is an additional pathway by which ribosome biogenesis may be regulated in neonatal cardiomyocytes. These results support the hypothesis that UBF is an important regulatory factor during the initiation and maintenance of the accelerated rate of rDNA transcription observed during neonatal cardiomyocyte hypertrophy mediated by both phorbol esters and endothelin-1.

Animals↗

PubMed1995

Hormone-regulated Ca2+ channel in rat hepatocytes revealed by whole cell patch clamp.

An inward current responsible for hormone regulated Ca2+ entry has been identified in cultured rat hepatocytes using whole cell patch clamp. Addition of 20 nM vasopressin or of 100 microM ATP induced the inward current, which could be observed more clearly after blocking an outward K+ current. This large outward K+ current, which appeared after addition of vasopressin or ATP, could be blocked either by replacing K+ with Cs+ in the external medium and in the pipette solution, or by simply including 0.5 microM apamin in the K(+)-containing external medium. The outward current appears to be carried by a Ca2+ activated K+ channel. In the presence of apamin, hepatocytes pretreated with vasopressin in a Ca(2+)-free media reveal an inward current on addition of external Ca2+ (5 mM). The current could also be elicited by addition of vasopressin when cells are preincubated in the presence of 5 mM external Ca2+. No current is seen on addition of Ca2+ in the absence of vasopressin. Initially, the inward current was ca 200-300 pA at -60 mV, but it declined rapidly over 3 min to ca 20 pA. The current approached zero, as an asymptote at positive potential, and appeared to be somewhat inwardly rectifying. Additions of 5 mM Mn2+ or 5 mM Ba2+ in place of Ca2+ produced little or no current. An inhibitor of ER Ca(2+)-ATPase, thapsigargin, could also trigger the cascade of events leading to plasma membrane conductance of Ca2+. The data suggest that hormone-stimulated Ca2+ entry into hepatocytes is mediated by a Ca(2+)-release activated channel highly specific for Ca2+. This is the first demonstration of such a channel in hepatocytes, though similar ones have been described in mast cells, in vascular endothelial cells and T-lymphocytes.

Adenosine Triphosphate↗

PubMed1995

Inhibition of ligand-induced activation of epidermal growth factor receptor tyrosine phosphorylation by curcumin.

We explored the regulation of epidermal growth factor (EGF)-mediated activation of EGF receptor (EGF-R) phosphorylation by curcumin (diferuloyl-methane), a recently identified kinase inhibitor, in cultured NIH 3T3 cells expressing human EGF-R. Treatment of cells with a saturating concentration of EGF for 5-15 min induced increased EGF-R tyrosine phosphorylation by 4- to 11-fold and this was inhibited in a dose- and time-dependent manner by up to 90% by curcumin, which also inhibited the growth of EGF-stimulated cells. There was no effect of curcumin treatment on the amount of surface expression of labeled EGF-R and inhibition of EGF-mediated tyrosine phosphorylation of EGF-R by curcumin was mediated by a reversible mechanism. In addition, curcumin also inhibited EGF-induced, but not bradykinin-induced, calcium release. These findings demonstrate that curcumin is a potent inhibitor of a growth stimulatory pathway, the ligand-induced activation of EGF-R, and may potentially be useful in developing anti-proliferative strategies to control tumor cell growth.

3T3 Cells↗

PubMed1995

[Ca2+]i transients in hypertensive and postinfarction myocytes.

Changes in intracellular calcium concentration ([Ca2+]i) in paced fura 2-loaded myocytes isolated from Sham, renovascular hypertensive (Hyp), and myocardial-infarcted (MI) rats were examined. Compared with controls, Hyp myocytes paced at physiological rates had similar systolic but elevated diastolic [Ca2+]i. By contrast, systolic [Ca2+]i was significantly lower and diastolic [Ca2+]i higher in MI myocytes. The different patterns of alterations in [Ca2+]i dynamics in Hyp and MI myocytes may partly explain predominantly diastolic dysfunction in hypertensive hearts and systolic dysfunction in hearts surviving MI. In the presence of 1 microM isoproterenol, both Hyp and MI myocytes had much lower systolic [Ca2+]i when compared with their respective controls. Isoproterenol restored the elevated diastolic [Ca2+]i in Hyp myocytes toward normal but had no effect on the intrinsic differences in diastolic [Ca2+]i between Sham and MI myocytes. The observation that isoproterenol lowers diastolic [Ca2+]i in Hyp myocytes toward normal may provide a cellular mechanism for the lack of efficacy of beta-adrenergic blockers to improve diastolic compliance in patients with hypertensive hypertrophic cardiomyopathy.

Adrenergic beta-Agonists↗

PubMed1995

Calcium currents in postinfarction rat cardiac myocytes.

Myocytes isolated from rat hearts that have suffered 35% myocardial infarction (MI) 3 wk prior have lower peak cytosolic Ca2+ concentration ([Ca2+]i) during contraction compared with Sham myocytes, a difference that is amplified by isoproterenol or high extracellular Ca2+ concentration ([Ca2+]o). To evaluate whether reduced [Ca2+]i in MI myocytes is due to decreased Ca2+ entry, we measured [3H]PN-200-110 [dihydropyridine (DHP)] binding and whole cell Ca2+ current (ICa). DHP binding decreased in both sarcolemmal vesicles and intact myocytes from hearts 3 wk after MI. In contrast, ICa was not different between Sham and MI myocytes incubated at 1.8 mM [Ca2+]o. At 5.0 mM [Ca2+]o, ICa increased similarly in Sham and MI myocytes. Steady-state voltage dependence of activation and inactivation were similar between Sham and MI myocytes, as were the fast- and slow-inactivation time constants. Isoproterenol (1 microM) significantly increased ICa in Sham but not in MI myocytes. Forskolin (10 microM) dibutyryl adenosine 3',5'-cyclic monophosphate (5 mM) significantly increased ICa in MI myocytes; the magnitude of ICa increase was similar to that observed in Sham myocytes. We conclude that 1) decreased systolic [Ca2+]i in MI myocytes was not due to reduced Ca2+ entry via L-type Ca2+ channels; 2) discrepancy between DHP binding (decrease) and ICa (no change) results may be explained by higher channel availability and/or increased long-opening modes (mode 2) in MI myocytes; 3) reduction in isoproterenol-induced [Ca2+]i increase in MI myocytes was partly due to decreased ICa, resulting in less Ca2+ release from sarcoplasmic reticulum; 4) the adenylate cyclase-protein kinase A signal-transduction pathway functioned normally in MI myocytes; and 5) decreased beta-adrenergic responsiveness in MI myocytes was likely due to altered coupling by G proteins.

Animals↗