Biomedical subjects

H Cheng

Publications and source records attributed to H Cheng.

At least 109 records · Page 6Linked to original sources

PubMed2000

Frequency-encoding Thr17 phospholamban phosphorylation is independent of Ser16 phosphorylation in cardiac myocytes.

Both Ser(16) and Thr(17) of phospholamban (PLB) are phosphorylated, respectively, by cAMP-dependent protein kinase (PKA) and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). PLB phosphorylation relieves cardiac sarcoplasmic reticulum Ca(2+) pump from inhibition by PLB. Previous studies have suggested that phosphorylation of Ser(16) by PKA is a prerequisite for Thr(17) phosphorylation by CaMKII and is essential to the relaxant effect of beta-adrenergic stimulation. To determine the role of Thr(17) PLB phosphorylation, we investigated the dual-site phosphorylation of PLB in isolated adult rat cardiac myocytes in response to beta(1)-adrenergic stimulation or electrical field stimulation (0. 1-3 Hz) or both. A beta(1)-adrenergic agonist, norepinephrine (10(-9)-10(-6) m), in the presence of an alpha(1)-adrenergic antagonist, prazosin (10(-6) m), selectively increases the PKA-dependent phosphorylation of PLB at Ser(16) in quiescent myocytes. In contrast, electrical pacing induces an opposite phosphorylation pattern, selectively enhancing the CaMKII-mediated Thr(17) PLB phosphorylation in a frequency-dependent manner. When combined, electric stimulation (2 Hz) and beta(1)-adrenergic stimulation lead to dual phosphorylation of PLB and exert a synergistic effect on phosphorylation of Thr(17) but not Ser(16). Frequency-dependent Thr(17) phosphorylation is closely correlated with a decrease in 50% relaxation time (t(50)) of cell contraction, which is independent of, but additive to, the relaxant effect of Ser(16) phosphorylation, resulting in hastened contractile relaxation at high stimulation frequencies. Thus, we conclude that in intact cardiac myocytes, phosphorylation of PLB at Thr(17) occurs in the absence of prior Ser(16) phosphorylation, and that frequencydependent Thr(17) PLB phosphorylation may provide an intrinsic mechanism for cardiac myocytes to adapt to a sudden change of heart rate.

Adenosine Triphosphatases↗

PubMed2000

Melting of the Earth's lithospheric mantle inferred from protactinium-thorium-uranium isotopic data

The processes responsible for the generation of partial melt in the Earth's lithospheric mantle and the movement of this melt to the Earth's surface remain enigmatic, owing to the perceived difficulties in generating large-degree partial melts at depth and in transporting small-degree melts through a static lithosphere. Here we present a method of placing constraints on melting in the lithospheric mantle using 231Pa-235U data obtained from continental basalts in the southwestern United States and Mexico. Combined with 230Th-238U data, the 231Pa-235U data allow us to constrain the source mineralogy and thus the depth of melting of these basalts. Our analysis indicates that it is possible to transport small melt fractions--of the order of 0.1%--through the lithosphere, as might result from the coalescence of melt by compaction owing to melting-induced deformation. The large observed 231Pa excesses require that the timescale of melt generation and transport within the lithosphere is small compared to the half-life of 231Pa (approximately 32.7 kyr). The 231Pa-230Th data also constrain the thorium and uranium distribution coefficients for clinopyroxene in the source regions of these basalts to be within 2% of one another, indicating that in this setting 230Th excesses are not expected during melting at depths shallower than 85 km.

Journal Article↗

PubMed2000

Inhibition of spontaneous beta 2-adrenergic activation rescues beta 1-adrenergic contractile response in cardiomyocytes overexpressing beta 2-adrenoceptor.

Cardiac-specific overexpression of the human beta(2)-adrenergic receptor (AR) in transgenic mice (TG4) enhances basal cardiac function due to ligand-independent spontaneous beta(2)-AR activation. However, agonist-mediated stimulation of either beta(1)-AR or beta(2)-AR fails to further enhance contractility in TG4 ventricular myocytes. Although the lack of beta(2)-AR response has been ascribed to an efficient coupling of the receptor to pertussis toxin-sensitive G(i) proteins in addition to G(s), the contractile response to beta(1)-AR stimulation by norepinephrine and an alpha(1)-adrenergic antagonist prazosin is not restored by pertussis toxin treatment despite a G(i) protein elevation of 1.7-fold in TG4 hearts. Since beta-adrenergic receptor kinase, betaARK1, activity remains unaltered, the unresponsiveness of beta(1)-AR is not caused by betaARK1-mediated receptor desensitization. In contrast, pre-incubation of cells with anti-adrenergic reagents such as muscarinic receptor agonist, carbachol (10(-5)m), or a beta(2)-AR inverse agonist, ICI 118,551 (5 x 10(-7)m), to abolish spontaneous beta(2)-AR signaling, both reduce the base-line cAMP and contractility and, surprisingly, restore the beta(1)-AR contractile response. The "rescued" contractile response is completely reversed by a beta(1)-AR antagonist, CGP 20712A. Furthermore, these results from the transgenic animals are corroborated by in vitro acute gene manipulation in cultured wild type adult mouse ventricular myocytes. Adenovirus-directed overexpression of the human beta(2)-AR results in elevated base-line cAMP and contraction associated with a marked attenuation of beta(1)-AR response; carbachol pretreatment fully revives the diminished beta(1)-AR contractile response. Thus, we conclude that constitutive beta(2)-AR activation induces a heterologous desensitization of beta(1)-ARs independent of betaARK1 and G(i) proteins; suppression of the constitutive beta(2)-AR signaling by either a beta(2)-AR inverse agonist or stimulation of the muscarinic receptor rescues the beta(1)-ARs from desensitization, permitting agonist-induced contractile response.

Adrenergic beta-Agonists↗

PubMed2000

Control of myeloid differentiation and survival by Stats.

Hematopoiesis involves a complex array of growth factors that regulate the survival and proliferation of immature progenitors, influence differentiation commitment, and modulate end-stage cell functions. This mini-review is focused on the role of Stat activation in the development of myeloid cells in response to hematopoietic cytokines. Much of the evidence implicating Stats in these cellular processes comes from studies of mutant cytokine receptors selectively uncoupled from Stat activation, dominant-inhibitory Stat mutants, and mice with targeted disruptions of Stat genes. Together these approaches provide strong evidence that Stat activation, particularly of Stat3 and Stat5, plays an important role in myeloid differentiation and survival. Oncogene (2000).

Animals↗

PubMed2000

Early human occupation of the Red Sea coast of Eritrea during the last interglacial.

The geographical origin of modern humans is the subject of ongoing scientific debate. The 'multiregional evolution' hypothesis argues that modern humans evolved semi-independently in Europe, Asia and Africa between 100,000 and 40,000 years ago, whereas the 'out of Africa' hypothesis contends that modern humans evolved in Africa between 200 and 100 kyr ago, migrating to Eurasia at some later time. Direct palaeontological, archaeological and biological evidence is necessary to resolve this debate. Here we report the discovery of early Middle Stone Age artefacts in an emerged reef terrace on the Red Sea coast of Eritrea, which we date to the last interglacial (about 125 kyr ago) using U-Th mass spectrometry techniques on fossil corals. The geological setting of these artefacts shows that early humans occupied coastal areas and exploited near-shore marine food resources in East Africa by this time. Together with similar, tentatively dated discoveries from South Africa this is the earliest well-dated evidence for human adaptation to a coastal marine environment, heralding an expansion in the range and complexity of human behaviour from one end of Africa to the other. This new, wide-spread adaptive strategy may, in part, signal the onset of modern human behaviour, which supports an African origin for modern humans by 125 kyr ago.

Adaptation, Physiological↗

PubMed2000

Efficient production of recombinant brazzein, a small, heat-stable, sweet-tasting protein of plant origin.

Brazzein is a 54-amino-acid sweet-tasting protein first isolated from the fruit of Pentadiplandra brazzeana Baillon found in West Africa. Brazzein, as isolated from the fruit, is 500 times sweeter than sucrose on a weight basis (9500 times sweeter on a per-molecule basis). A minor component of brazzein from fruit, des-pGlu1-brazzein, has 53 amino acid residues and has twice the sweetness of the parent protein. We have designed a gene for des-pGlu1- brazzein that incorporates codons that are optimal for protein production in Escherichia coli. Production of brazzein from the chemically synthesized gene resulted in recombinant protein with sweetness similar to that of brazzein isolated from the original source. The best yields were achieved by producing brazzein as a fusion with staphylococcal nuclease with a designed cyanogen bromide cleavage site. Because of its intense sweetness and stability at high pH and temperature, brazzein is an ideal system for investigating the chemical and structural requirements involved in sweet-taste properties. This efficient protein production system for brazzein will facilitate such investigations.

Base Sequence↗

PubMed2000

Involvement of multiple intracellular release channels in calcium sparks of skeletal muscle.

In many types of muscle, intracellular Ca(2+) release for contraction consists of brief Ca(2+) sparks. Whether these result from the opening of one or many channels in the sarcoplasmic reticulum is not known. Examining massive numbers of sparks from frog skeletal muscle and evaluating their Ca(2+) release current, we provide evidence that they are generated by multiple channels. A mode is demonstrated in the distribution of spark rise times in the presence of the channel activator caffeine. This finding contradicts expectations for single channels evolving reversibly, but not for channels in a group, which collectively could give rise to a stereotyped spark. The release channel agonists imperatoxin A, ryanodine, and bastadin 10 elicit fluorescence events that start with a spark, then decay to steady levels roughly proportional to the unitary conductances of 35%, 50%, and 100% that the agonists, respectively, promote in bilayer experiments. This correspondence indicates that the steady phase is produced by one open channel. Calculated Ca(2+) release current decays 10- to 20-fold from spark to steady phase, which requires that six or more channels be open during the spark.

Animals↗

PubMed2000

Evidence that ThiI, an enzyme shared between thiamin and 4-thiouridine biosynthesis, may be a sulfurtransferase that proceeds through a persulfide intermediate.

ThiI is an enzyme common to the biosynthetic pathways leading to both thiamin and 4-thiouridine in tRNA. Comparison of the ThiI sequence with protein sequences in the data bases revealed that the Escherichia coli enzyme contains a C-terminal extension displaying sequence similarity to the sulfurtransferase rhodanese. Cys-456 of ThiI aligns with the active site cysteine residue of rhodanese that transiently forms a persulfide during catalysis. We investigated the functional importance of this sequence similarity and discovered that, like rhodanese, ThiI catalyzes the transfer of sulfur from thiosulfate to cyanide. Mutation of Cys-456 to alanine impairs this sulfurtransferase activity, and the C456A ThiI is incapable of supporting generation of 4-thiouridine in tRNA both in vitro and in vivo. We therefore conclude that Cys-456 of ThiI is critical for activity and propose that Cys-456 transiently forms a persulfide during catalysis. To accommodate this hypothesis, we propose a general mechanism for sulfur transfer in which the terminal sulfur of the persulfide first acts as a nucleophile and is then transferred as an equivalent of S(2-) rather than S(0).

Amino Acid Sequence↗

PubMed2000

Perceived parental behaviour, self-esteem and happiness.

BACKGROUND: This study set out to determine to what extent recalled parental rearing styles (authoritarian, authoritativeness, permissiveness), personality (extraversion, neuroticism, psychoticism, lie), and self-esteem predicted self-rated happiness in a normal, nonclinical, population of young people in their late teens and early 20s. METHODS: Each participant completed a few questionnaires: the Eysenck Personality Questionnaire (revised), the Rosenberg Self-Esteem Scale, the Parental Authority Questionnaire and the Oxford Happiness Inventory. It was predicted that sex, extraversion, neuroticism, self-esteem and both maternal and paternal authoritativeness would be significant predictors of happiness. RESULTS: Regressional and path analysis showed self-esteem to be the most dominant and powerful predictor of happiness. The effect of sex on happiness was moderated by neuroticism, which related to self-esteem, which directly influenced happiness. Stability, extraversion and maternal authoritativeness were significant predictors of self-esteem accounting for one-third of the variance. CONCLUSION: The results are considered in terms of the distinct literature on the relation between personality and happiness and on the relation between parental styles and self-esteem. Self-esteem was both a direct and a moderator variable for young people's self-reported happiness. Extraversion had both direct and indirect predictive power of happiness, whereas neuroticism predicted happiness mediating through self-esteem. Maternal authoritativeness was the only direct predictor of happiness when paternal and maternal rearing styles were examined together, suggesting that a reasonable discipline exercised by mothers towards their children was particularly beneficial in enhancing the offsprings' self-esteem.

Adolescent↗

PubMed2000

Connexin 43 expression is downregulated in raft cultures of human keratinocytes expressing the human papillomavirus type 16 E5 protein.

A decrease in gap junction-mediated cell-to-cell communication has previously been observed in monolayer cultures of human keratinocytes (HaCaT cells) expressing the human papillomavirus type 16 E5 (HPV16 E5) gene and attributed to the reduced phosphorylation of connexin 43, the most abundant connexin in HaCaT cells. In line with this observation, we have now analyzed the effect of HPV16 E5 on connexin 43 expression in raft cultures produced by transfected HaCaT cells. These keratinocytes transcribe HPV16 E5 under the control of a dexamethasone-inducible promoter. Our results show that treatment with dexamethasone leads to an almost complete disappearance of connexin 43 in rafts expressing the E5 gene but not in control rafts. In our study we discuss the possible effects of this downregulation on cell-cell communication and cellular malignant transformation.

Cell Culture Techniques↗

PubMed2000

G(i)-dependent localization of beta(2)-adrenergic receptor signaling to L-type Ca(2+) channels.

A plausible determinant of the specificity of receptor signaling is the cellular compartment over which the signal is broadcast. In rat heart, stimulation of beta(1)-adrenergic receptor (beta(1)-AR), coupled to G(s)-protein, or beta(2)-AR, coupled to G(s)- and G(i)-proteins, both increase L-type Ca(2+) current, causing enhanced contractile strength. But only beta(1)-AR stimulation increases the phosphorylation of phospholamban, troponin-I, and C-protein, causing accelerated muscle relaxation and reduced myofilament sensitivity to Ca(2+). beta(2)-AR stimulation does not affect any of these intracellular proteins. We hypothesized that beta(2)-AR signaling might be localized to the cell membrane. Thus we examined the spatial range and characteristics of beta(1)-AR and beta(2)-AR signaling on their common effector, L-type Ca(2+) channels. Using the cell-attached patch-clamp technique, we show that stimulation of beta(1)-AR or beta(2)-AR in the patch membrane, by adding agonist into patch pipette, both activated the channels in the patch. But when the agonist was applied to the membrane outside the patch pipette, only beta(1)-AR stimulation activated the channels. Thus, beta(1)-AR signaling to the channels is diffusive through cytosol, whereas beta(2)-AR signaling is localized to the cell membrane. Furthermore, activation of G(i) is essential to the localization of beta(2)-AR signaling because in pertussis toxin-treated cells, beta(2)-AR signaling becomes diffusive. Our results suggest that the dual coupling of beta(2)-AR to both G(s)- and G(i)-proteins leads to a highly localized beta(2)-AR signaling pathway to modulate sarcolemmal L-type Ca(2+) channels in rat ventricular myocytes.

Animals↗

PubMed2000

Birth control method choice and use of barrier methods for sexually transmitted disease prevention among low-income African-American women.

In a prospective study of 1122 women attending a sexually transmitted disease (STD) clinic in Alabama, consistent use of the male condom and vaginal microbicide/spermicides was promoted to reduce STD risk. This analysis evaluated: 1) baseline characteristics that may influence birth control method choice; and 2) the association of birth control method and other baseline characteristics with consistency of barrier use during follow up. Birth control method was associated with sociodemographic variables, sexual, and reproductive history. Women who adopted user-independent methods (tubal ligation, implants, injectable hormones) appear to have completed their family plan. Oral contraceptive users were of higher socioeconomic status and at lower STD risk. Barrier method users and women who used no method were young and at higher STD risk. Consistency of condom/spermicide use increased in all groups. Barrier method users were more likely than other women to use condoms and spermicides during the study. Women who used no birth control method at baseline experienced the largest increase in barrier use during follow up, although their barrier use rates were lower than in other groups. The synergism between the intention to prevent pregnancy and the intention to prevent STD should be considered in the design of interventions promoting condom use.

Adolescent↗

PubMed2000

The South Asian cataract management study: complications, vision outcomes, and corneal endothelial cell loss in a randomized multicenter clinical trial comparing intracapsular cataract extraction with and without anterior chamber intraocular lens implantation.

OBJECTIVE: To determine clinical outcomes of primary intracapsular cataract surgery with and without implantation of anterior chamber lenses. DESIGN: A multicenter randomized clinical trial. PARTICIPANTS: One thousand two hundred twenty-nine male and female patients 40-75 years of age with senile cataract. METHODS: Study patients were recruited from screening eye camps and outpatient clinics. Randomization to the two treatment groups was performed after screening for predetermined inclusion and exclusion criteria. Demographics, visual acuity, intraocular pressures, and corneal endothelial cell data were recorded before surgery and at 6 weeks, 12 months, and 24 months after surgery. Monitoring of the study was secured by a standardized image documentation procedure on all patients using the IMAGEnet digital imaging system. Analysis of corneal endothelial cell images was performed with the Cell Soft software (Topcon Corporation, Japan). MAIN OUTCOME MEASURES: Visual acuity and central corneal endothelial cell loss. RESULTS: The patients were randomized to intraocular lens (IOL; n = 616) and no IOL (n = 613) implantation. Surgical complications were reported in 177 (14.4%) patients (IOL = 14.8%; no IOL = 14.0%). The most frequent complication observed was vitreous loss which occurred in 10.3% of eyes (IOL = 11.2%; no IOL = 9.5%). At the final examination (2 years after surgery), 88% of the operated eyes had a best corrected vision of 6/18 or better (IOL = 88.8%; no IOL = 86.6%). Analysis of corneal endothelial cell data showed a small but significantly greater cell loss 6 weeks after surgery in eyes with IOL compared with those without IOL, but no overall difference was found between the treatment groups in the long term follow-up. CONCLUSIONS: The findings indicate that there is a rationale for the use of anterior chamber intraocular lenses in primary intracapsular cataract surgery.

Adult↗

PubMed2000

Validity and coverage of estimates of relative accuracy.

PURPOSE: Studies comparing test accuracy often restrict the confirmation procedure to subjects classified as positive by either test. Relative sensitivity (RSN) and relative false-positive rate (RFP) are two estimable comparative measures of accuracy. This article evaluates the influence of sample size, disease prevalence, and test accuracy on the validity of point estimates of RSN and RFP, and on the coverage of their confidence intervals (CI). METHODS: For each combination of sample size, disease prevalence, test accuracy, and interdependence between tests 1,000 samples were generated using computer simulations. The percent bias in the RSN and RFP estimates was measured by comparing the means of the 1,000 values computed in each simulation (log-transformed) with their theoretical values. Coverage of the estimated CI was measured by computing the proportion that actually included the theoretical values. Application of these methods was illustrated with data from a study comparing mammography and physical examination in screening for breast cancer. RESULTS: RSN estimates were valid if the true number of diseased cases exceeded 30, and RFP estimates were valid if the number of nondiseased subjects exceeded 200. When the numbers of diseased and nondiseased subjects exceeded 150 each, the 95% CI of RSN and RFP provided adequate coverage of the parameters (95 +/- 2%). CONCLUSION: Sample size is the most important variable for the validity and coverage of RSN and RFP estimates. For small samples, validity and coverage of RSN and RFP also depend on the accuracy of each test and on the degree of interdependence between the tests.

Adult↗

PubMed2000

Cyclic core dendrimer as a new kind of vector for gene transfer into mammalian cells.

Cyclic core dendritic polymer is a new type of synthetic polymers. The ability of generation 4 of the dendrimer with a core of 1,4,7,10-tetraazacyclododecane to function as an effective gene delivery vector was investigated. Results from fluorescence in situ hybridization (FISH) show that the pCH 110 plasmid DNA was transferred into human small intestine cancer metastatic ascites (HICMA) cells induced by this kind of dendrimer as a vector. The transferred LacZ, GFP and luciferase genes were highly expressed in the transfected HICMA, COS-7 and 293 cells. These studies demonstrate that the dendrimer can transfect mammalian cells in vitro which offers an alternatively efficient method for mammalian gene transfer.

Animals↗

PubMed2000

Effects of Ca2+ on the activity and stability of methanol dehydrogenase.

The effects of exogenously added Ca2+ on the enzymatic activity and structural stability of methanol dehydrogenase were studied for various Ca2+ concentrations. Methanol dehydrogenase activity increased significantly with increasing concentration of Ca2+, approaching saturation at 200 mM Ca2+. The effect of Ca2+ on the activation of MDH was time dependent and Ca2+ specific and was due to binding of the metal ions to the enzyme. Addition of increasing concentration of Ca2+ caused a decrease of the intrinsic tryptophan fluorescence intensity in a concentration-dependent manner to a minimum at 200 mM, but with no change in the fluorescence emission maximum wavelength or the CD spectra. The results revealed that the activation of methanol dehydrogenase by Ca2+ occurred concurrently with the conformational change. In addition, exogenously bound Ca2+ destabilized MDH. The potential biological significance of these results is discussed.

Alcohol Oxidoreductases↗

PubMed2000

Mechanisms of AVP-induced glucagon release in clonal alpha-cells in-R1-G9: involvement of Ca(2+)-dependent and -independent pathways.

1. The mechanisms underlying AVP-induced increase in [Ca(2+)](i) and glucagon release in clonal alpha-cells In-R1-G9 were investigated. 2. AVP increased [Ca(2+)](i) and glucagon release in a concentration-dependent manner. After the administration of AVP, glucagon was released within 30 s, quickly reached the maximum within 2 min, and maintained a steady-state concentration for at least 15 min. 3. In Ca(2+)-containing medium, AVP increased [Ca(2+)](i) in a biphasic pattern; a peak followed by a sustained plateau. In Ca(2+)-free medium, the Ca(2+) response to AVP became monophasic with lower amplitude and no plateau. Both the basal and AVP-induced glucagon releases were lower in the absence than in the presence of extracellular Ca(2+). When [Ca(2+)](i) was stringently deprived by BAPTA, a Ca(2+) chelator, AVP still significantly increased glucagon release. 4. Pretreatment with thapsigargin, a microsomal Ca(2+) ATPase inhibitor, abolished both the Ca(2+) peak and sustained plateau. 5.AVP increased intracellular concentration of IP(3). 6. U-73122 (8 microM), a phospholipase C inhibitor, abolished AVP-induced increases in [Ca(2+)](i), but only reduced AVP-induced glucagon release by 39%. 7. Pretreatment with nimodipine, an L-type Ca(2+) channel blocker failed to alter AVP-induced glucagon release or increase in [Ca(2+)](i). 8. The results suggest that AVP causes glucagon release through both Ca(2+)-dependent and -independent pathways. For the Ca(2+)-dependent pathway, the G(q) protein activates phospholipase C, which catalyzes the formation of IP(3). IP(3) induces Ca(2+) release from the endoplasmic reticulum, which, in turn, triggers Ca(2+) influx. Both Ca(2+) release and Ca(2+) influx may contribute to AVP-induced glucagon release.

Amino Acid Chloromethyl Ketones↗

PubMed2000

Electrophysiological effects of protopine in cardiac myocytes: inhibition of multiple cation channel currents.

Protopine (Pro) from Corydalis tubers has been shown to have multiple actions on cardiovascular system, including anti-arrhythmic, anti-hypertensive and negative inotropic effects. Although it was thought that Pro exerts its actions through blocking Ca(2+) currents, the electrophysiological profile of Pro is unclear. The aim of this study is to elucidate the ionic mechanisms of Pro effects in the heart. In single isolated ventricular myocytes from guinea-pig, extracellular application of Pro markedly and reversibly abbreviates action potential duration, and decreases the rate of upstroke (dV/dt)(max), amplitude and overshoot of action potential in a dose-dependent manner. Additionally, it produces a slight, but significant hyperpolarization of the resting membrane potential. Pro at 25, 50 and 100 microM reduces L-type Ca(2+) current (I(Ca,L)) amplitude to 89.1, 61.9 and 45.8% of control, respectively, and significantly slows the decay kinetics of I(Ca,L) at higher concentration. The steady state inactivation of I(Ca,L) is shifted negatively by 5.9 - 7.0 mV (at 50 - 100 microM Pro), whereas the voltage-dependent activation of I(Ca,L) remains unchanged. In contrast, Pro at 100 microM has no evident effects on T-type Ca(2+) current (I(Ca,T)). In the presence of Pro, both the inward rectifier (I(K1)) and delayed rectifier (I(K)) potassium currents are variably inhibited, depending on Pro concentrations. Sodium current (I(Na)), recorded in low [Na(+)](o) (40 mM) solution, is more potently suppressed by Pro. At 25 microM, Pro significantly attenuated I(Na) at most of the test voltages (-60 approximately +40 mV, with a 53% reduction at -30 mV. Thus, Pro is not a selective Ca(2+) channel antagonist. Rather, it acts as a promiscuous inhibitor of cation channel currents including I(Ca,L), I(K), I(K1) as well as I(Na). These findings may provide some mechanistic explanations for the therapeutic actions of Pro in the heart.

Action Potentials↗