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Biomedical subjects

R H Lee

Publications and source records attributed to R H Lee.

At least 19 recordsLinked to original sources
PubMed2006

The prevalence of intrahepatic cholestasis of pregnancy in a primarily Latina Los Angeles population.

OBJECTIVE: To establish the prevalence of intrahepatic cholestasis of pregnancy (ICP) in a primarily Latina population in the United States. STUDY DESIGN: Over a period of 16 months, a convenience sample of subjects admitted to labor and delivery in the third trimester was enrolled. Each subject completed a questionnaire rating their severity of pruritus on a numeric scale of 1 to 10. Serum was analyzed via radioimmunoassay for total bile acid concentration. ICP was defined as pruritus score >4 and a total serum bile acid concentration of >or=20 micromol/l. Ethnicity was determined from hospital record demographic data. RESULTS: All invited participants enrolled in the study. Three hundred and forty subjects were enrolled. Three hundred and sixteen subjects (93%) were identified as Latina. The serum bile acid concentration range for the entire study population was 1 to 580 micromol/l with a mean of 10.4+/-34.9 micromol/l. Twenty-four (7.1%) subjects had a serum bile acid concentration >or=20 micromol/l. A pruritus score >4 was found in 19.7% (67/340). Of the 24 subjects with a bile acid concentration >or=20 micromol/l, 19 also had a pruritus score >4. Thus, the prevalence of ICP in this population was 5.6% (19/340). In subjects with ICP, the mean serum bile acid concentration was 89.5+/-124.0 micromol/l. When controlling for confounders, women with ICP were associated with higher rates of chorioamnionitis (P=0.043) and their fetuses had higher rates of thick meconium (P=0.053). CONCLUSIONS: The overall prevalence of ICP in this population was 5.6%, 10 to 100 times higher than previously reported data from the United States. Larger studies of perinatal morbidity examining the diagnostic criteria of cholestasis need to be conducted.

Adult↗
PubMed2006

Essential role of the persistent sodium current in spike initiation during slowly rising inputs in mouse spinal neurones.

Spinal motoneurons, like many neurons, respond with repetitive spiking to sustained inputs. The afterhyperpolarization (AHP) that follows each spike, however, decays relatively slowly in motoneurons. The slow depolarization during this decay should allow sodium (Na+) channel inactivation to keep up with its activation and thus should prevent initiation of the next spike. We hypothesized that the persistent component of the total Na+ current provides the mechanism that generates a rate of rise sufficiently rapid to generate a spike. In large cultured spinal neurons, presumed to be primarily motoneurons, inhibition of persistent sodium current (NaP) by the drug riluzole at low concentrations resulted in a loss of repetitive firing. However, cells remained fully capable of producing spikes to transient inputs. These effects of riluzole were not due to insufficient depolarization, enhancement of the AHP, or sustained Na+ channel inactivation. To further test this hypothesis, computer simulations were performed with a kinetic Na+ channel model that provided greater independent control of NaP relative to transient Na+ current (NaT) than that provided by riluzole administration. The model was tuned to generate substantial NaP and exhibited good repetitive firing to slowly rising inputs. When NaP was sharply reduced without significantly altering NaT, the model reproduced the effects of riluzole administration, inducing failure of repetitive firing but allowing single spikes in response to sharp transients. These results strongly support the essential role of NaP in spike initiation to slow inputs in spinal neurons. NaP may play a fundamental role in determining how a neuron responds to sustained inputs.

Action Potentials↗
PubMed2005

Roles of NF-kappaB and bcl-2 in two differential modes of cell death of mouse cortical collecting duct cells.

Recent data have implicated nuclear factor-kappaB (NF-kappaB) and Bcl-2 in the regulation of apoptotic and necrotic cell death in various cells. However, mechanisms of their effects on cell death of renal epithelial cells are not clear. First, we investigated the effect of specific inhibition of NF-kappaB and overexpression of Bcl-2 on necrotic cell death induced by hydrogen peroxide or cisplatin in renal collecting duct cells. M-1 cells, which were derived from outer cortical collecting duct, were stably transfected with the non-phosphorylatable mutant of inhibitory-kappaBalpha (I-kappaBalpha) and Bcl-2. Overexpression of I-kappaBalpha and Bcl-2 did not affect cisplatin-induced necrotic cell death, but overexpression of I-kappaBalpha significantly decreased H2O2-induced cell death. Regarding apoptotic cell death induced by cisplatin, serum deprivation and contact inhibition was increased by overexpression of I-kappaBalpha, whereas overexpression of bcl-2 inhibited the apoptotic cell death. I-kappaBalpha overexpression increased Bax expression and decreased cIAP-1 and -2 expression compared to vector-transfected cells, but did not alter SAPK/JNK activity in the presence or absence of cisplatin. NF-kappaB activity was significantly higher in bcl-2-overexpressing cells than in control cells. These data show that activation of NF-kappaB mediates H2O2-induced necrotic injury, but inhibits apoptotic cell death in renal collecting duct cells, and that Bcl-2 selectively protects apoptotic cell death in M-1 cells.

Animals↗
PubMed2004

Effects of peripheral benzodiazepine receptor ligands on proliferation and differentiation of human mesenchymal stem cells.

The peripheral benzodiazepine receptor (PBR) has been known to have many functions such as a role in cell proliferation, cell differentiation, steroidogenesis, calcium flow, cellular respiration, cellular immunity, malignancy, and apoptosis. However, the presence of PBR has not been examined in mesenchymal stem cells. In this study, we demonstrated the expression of PBR in human bone marrow stromal cells (hBMSCs) and human adipose stromal cells (hATSCs) by RT-PCR and immunocytochemistry. To determine the roles of PBR in cellular functions of human mesenchymal stem cells (hMSCs), effects of diazepam, PK11195, and Ro5-4864 were examined. Adipose differentiation of hMSCs was decreased by high concentration of PBR ligands (50 microM), whereas it was increased by low concentrations of PBR ligands (<10 microM). PBR ligands showed a biphasic effect on glycerol-3-phosphate dehydrogenase (GPDH) activity. High concentration of PBR ligands (from 25 to 75 microM) inhibited proliferation of hMSCs. However, clonazepam, which does not have an affinity to PBR, did not affect adipose differentiation and proliferation of hMSCs. The PBR ligands did not induce cell death in hMSCs. PK11195 (50 microM) and Ro5-5864 (50 microM) induced cell cycle arrest in the G(2)/M phase. These results indicate that PBR ligands play roles in adipose differentiation and proliferation of hMSCs.

Anti-Anxiety Agents↗
PubMed2003

Influence of active dendritic currents on input-output processing in spinal motoneurons in vivo.

The extensive dendritic tree of the adult spinal motoneuron generates a powerful persistent inward current (PIC). We investigated how this dendritic PIC influenced conversion of synaptic input to rhythmic firing. A linearly increasing, predominantly excitatory synaptic input was generated in triceps ankle extensor motoneurons by slow stretch (duration: 2-10 s) of the Achilles tendon in the decerebrate cat preparation. The firing pattern evoked by stretch was measured by injecting a steady current to depolarize the cell to threshold for firing. The effective synaptic current (I(N), the net synaptic current reaching the soma of the cell) evoked by stretch was measured during voltage clamp. Hyperpolarized holding potentials were used to minimize the activation of the dendritic PIC and thus estimate stretch-evoked I(N) for a passive dendritic tree (I(N,PASS)). Depolarized holding potentials that approximated the average membrane potential during rhythmic firing allowed strong activation of the dendritic PIC and thus resulted in marked enhancement of the total stretch-evoked I(N) (I(N,TOT)). The net effect of the dendritic PIC on the generation of rhythmic firing was assessed by plotting stretch-evoked firing (strong PIC activation) versus stretch-evoked I(N,PASS) (minimal PIC activation). The gain of this input-output function for the neuron (I-O(N)) was found to be ~2.7 times as high as for the standard injected frequency current (F-I) function in low-input conductance neurons. However, about halfway through the stretch, firing rate tended to become constant, resulting in a sharp saturation in I-O(N) that was not present in F-I. In addition, the gain of I-O(N) decreased sharply with increasing input conductance, resulting in much lower stretch-evoked firing rates in high-input conductance cells. All three of these phenomena (high initial gain, saturation, and differences in low- and high-input conductance cells) were also readily apparent in the differences between stretch-evoked I(N,TOT) and I(N, PASS) and thus could be accounted for by the activation of the dendritic PIC. As a result, stretch-evoked I(N,TOT) and F-I provided an accurate prediction of the overall change in stretch-evoked firing. However, in about half of the low-input conductance cells, the rate of rise of firing in response to stretch was not smoothly graded but instead consisted of a rapid surge. Stretch-evoked I(N,TOT) was always smoothly graded. This suggests that although stretch-evoked I(N,TOT) can be used to predict the overall change in firing, prediction of the dynamics of firing may be less accurate.

Animals↗
PubMed2001

Cisplatin-induced apoptosis by translocation of endogenous Bax in mouse collecting duct cells.

cis-platinum(II) (cis-diammine dichloroplatinum; cisplatin) is a potent antitumor compound that is widely used for the treatment of many malignancies. An important side-effect of cisplatin is nephrotoxicity, which results from injury to renal tubular epithelial cells and can be manifested as either acute renal failure or a chronic syndrome characterized by renal electrolyte wasting. Recently, apoptosis has been recognized as an important mechanism of cell death mediating the antitumor effect of cisplatin. This study was undertaken to examine the mechanisms of cell death induced by cisplatin in M-1 cells, which were derived from the outer cortical collecting duct cells of SV40 transgenic mice. Treatment of M-1 cells with high concentrations of cisplatin (0.5 and 1 mM) for 2 hr led to necrotic cell death, whereas a 24-hr treatment with 5-20 microM cisplatin led to apoptosis. Antioxidants protected against cisplatin-induced necrosis, but not apoptosis, indicating that reactive oxygen species play a role in mediating necrosis but not apoptosis induced by cisplatin and that the mechanism of cell death induced by cisplatin is concentration dependent. The low concentrations of cisplatin, which induced apoptosis in M-1 cells, did not affect the expression levels of Bcl-2-related proteins and did not activate c-Jun NH2-terminal kinase (SAPK/JNK). Cisplatin induced the translocation of endogenous Bax from the cytosolic to the membrane fractions and, subsequently, the release of cytochrome c. Overexpression of Bcl-2 blocked cisplatin-induced apoptosis and Bax translocation. These observations suggest that the subcellular redistribution of Bax is a critical event in the apoptosis induced by cisplatin.

Animals↗
PubMed2001

Nitric oxide in the healing wound: a time-course study.

INTRODUCTION: We studied the time course of nitric oxide expression in the healing wound and the cell populations responsible for its synthesis. METHODS: Twenty four Lewis rats underwent subcutaneous implantation of polyvinyl alcohol sponges. Rats were sacrificed in groups of three on days 1, 3, 5, 7, 10, 14, and 35 after wounding. The conversion of 3H-labeled arginine to 3H-labeled citrulline, with or without N(G)-L-monomethyl-arginine (L-NMMA) in harvested sponges, was measured. Nitrate/nitrite (NOx) in plasma and wound fluid was quantified by Greiss reaction. Inducible nitric oxide synthase (iNOS) gene expression was determined by Northern analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). Inducible NOS was identified in specific wound cell populations by dual-label flow cytometry. RESULTS: Nitric oxide synthase (NOS) activity peaked at 24 h after wounding (37.7 +/- 0.9 micromol citrulline per milligram sponge), with a steady decline thereafter. Percentage inhibition of NOS activity by l-NMMA was highest on days 1-7 (70-80%). This declined to 50% by day 10 and to 25% by days 14-35. The iNOS gene expression paralleled NOS biochemical activity. RT-PCR confirmed low-level expression up to 10 days after wounding. Plasma NOx levels remained within a narrow range of 22.6 +/- 1.3 to 29.3 +/- 1.5 microM throughout the postwounding period, while corresponding levels in wound fluid (microM) increased steadily from 27 +/- 3.8 on day 1 to 107.2 +/- 10.0 on day 14. Inducible NOS expression was detectable by fluorescence-activated cell sorting in wound macrophages on days 1 and 3 after wounding. CONCLUSIONS: Our findings suggest maximal NOS activity early in cutaneous wound healing, with sustained production up to 10 days after wounding. NOS biochemical activity was paralleled by iNOS gene expression. Plasma NOx remained constant, while wound fluid NOx increased steadily to peak at day 14. Wound macrophages appear to be a source of nitric oxide production in the early phase of wound healing.

Animals↗
PubMed2001

System effects of the Kansas Mental Health Reform Act of 1991.

This paper analyzes the impact of the Kansas Mental Health Reform Act on client outcomes. The Act is of general interest because it reflects a trial of greater accountability without major changes in financial incentives. It made Community Mental Health Centers [CMHCs] gatekeepers that were accountable for services for adults with severe and persistent mental illnesses. The Act sought reductions in hospitalizations rates, expanded use of community support services, and increased independent living. The structure of the Act and Client Status Reports allow rigorous examination of these outcomes. The number of clients served increased significantly. Even though hospital days fell by 23%, there is no clear evidence that the Act itself reduced hospital days per client. The proportion of community support program clients residing independently rose significantly; the proportion participating meaningfully in the labor market fell. The goals of the Act were realized overall, but the performance of CMHCs varied considerably.

Activities of Daily Living↗
PubMed2001

Growth and nutrition of Chinese vegetarian children in Hong Kong.

OBJECTIVE: The study investigated the nutritional status of Chinese lacto-ovo-vegetarian children aged 4-14 years. METHODOLOGY: Dietary intake over 7 days was assessed using a computer program, previously used for a local population-based dietary survey. Anthropometric measurements were made and fasting venous blood was examined for serum lipids, haematological data, iron, vitamin B12 and folate status. Bone mineral density (BMD) of the spine (L2 - L4) was measured as a reflection of calcium status. RESULTS: Fifty-one lacto-ovo-vegetarians aged 4-14 years were investigated. The mean +/- standard deviation (SD) daily energy intake was 1600 +/- 425 kcal. The mean (+/- SD) daily protein intake was 1.6 +/- 0.6 g/kg bodyweight which met the United States recommended dietary allowance. Compared to that of the local omnivore diet, the vegetarian diet was closer to the recommended healthy diet with lower fat (20-23%), more fibre (5.8-8.7 g/day) and better polyunsaturated to saturated fatty acid ratio (1.0-1.1). Growth and BMD of the vegetarian children were comparable to the general omnivore population. Two children had iron deficiency and two children had anaemia. The calcium status, as reflected by the BMD, was not impaired. Serum folate and vitamin B12 were within the normal range. Six (25%) boys and four (15%) girls were obese. Three boys had hyperlipidaemia. CONCLUSIONS: A Hong Kong Chinese vegetarian diet appears healthy, providing adequate iron and vitamin B12 nutrition, but the prevalence of obesity was high.

Adolescent↗
PubMed2001

Leaf senescence in rice plants: cloning and characterization of senescence up-regulated genes.

To identify senescence-associated genes (SAGs) in rice leaves, senescence was induced by transferring rice seedlings into darkness. Senescence up-regulated cDNAs were obtained by PCR-based subtractive hybridization. Among 14 SAG clones characterized, 11 were found to be associated with both dark-induced and natural leaf senescence. Three clones were associated only with dark-induced leaf senescence. The possible physiological roles of these SAGs during rice leaf senescence are discussed.

Cloning, Molecular↗
PubMed2001

Essential role of a fast persistent inward current in action potential initiation and control of rhythmic firing.

In spinal motoneurons in an in vivo preparation, we investigated the relationship between a fast persistent inward current located in or near the soma and the capacity of these cells to fire rhythmically. The fast persistent current could be markedly reduced by prolonged depolarization. Modest reductions resulted in profound changes in the slope of the frequency-current relationship. At greater reduction levels, rhythmic firing failed and could not be restored by increasing injected current. However, fully formed spikes still occurred in a slow, uncoordinated fashion, suggesting that the fast inactivating Na(+) currents that generate the spike itself remained unchanged. Consequently, the fast persistent inward current, which may be primarily generated by persistent Na(+) channels, appears to be essential for initiation of spikes during rhythmic firing. Additionally, it appears that the fast persistent current plays a major role in setting the frequency-current gain.

Action Potentials↗
PubMed2000

Adjustable amplification of synaptic input in the dendrites of spinal motoneurons in vivo.

The impact of neuromodulators on active dendritic conductances was investigated by the use of intracellular recording techniques in spinal motoneurons in the adult cat. The well known lack of voltage control of dendritic regions during voltage clamp applied at the soma was used to estimate dendritic amplification of a steady monosynaptic input generated by muscle spindle Ia afferents. In preparations deeply anesthetized with pentobarbital, Ia current either decreased with depolarization or underwent a modest increase at membrane potentials above -40 mV. In unanesthetized decerebrate preparations (which have tonic activity in axons originating in the brainstem and releasing serotonin or norepinephrine), active dendritic currents caused strong amplification of Ia input. In the range of -50 to -40 mV, peak Ia current was over four times as large as that in the pentobarbital-anesthetized preparations. Exogenous administration of a noradrenergic agonist in addition to the tonic activity further enhanced amplification (sixfold increase). Amplification was not seen in preparations with spinal transections. Overall, the dendritic amplification with moderate or strong neuromodulatory drive was estimated to be large enough to allow the motoneurons innervating slow muscle fibers to be driven to their maximum force levels by remarkably small synaptic inputs. In these cells, the main role of synaptic input may be to control the activation of a highly excitable dendritic tree. The neuromodulatory control of synaptic amplification provides motor commands with the potential to adjust the level of amplification to suit the demands of different motor tasks.

Afferent Pathways↗
PubMed2000

Changes in expression of sodium cotransporters and aquaporin-2 during ischemia-reperfusion injury in rabbit kidney.

Ischemic renal injury is associated with defects in transport functions of the proximal tubules and urinary concentration ability. To determine whether alterations in expression of various transporter genes contribute to an impairment in renal functions, the expression of various solute transport genes was analyzed in renal cortex and medulla of rabbits with ischemic acute renal failure. Rabbits were subjected to 60 min of renal pedicle clamping followed by 24, 48, or 72 h of reperfusion. Urine volume and glomerular filtration rate were markedly decreased, which were accompanied by an increase in serum creatinine level and fraction Na+ excretion. Glucosuria and phosphaturia were evident during reperfusion periods. These alterations in renal functions were persisted to 72 h after reperfusion. The Na+-dependent uptakes of glucose and phosphate by brush border membrane vesicles were inhibited by 24 h of reperfusion. mRNA levels for Na+-glucose, Na+-phosphate, and Na+-succinate cotransporter analyzed by RT-PCR were not changed by 60 min of ischemia alone, but were significantly reduced by 24 h of reperfusion. mRNA levels for apical Na+-K+-2Cl- cotransporter, NaCl cotransporter, and turea transporter in the medulla were not changed during reperfusion. Protein levels for AQP2 in the medulla, but not AQP1 in the cortex, analyzed by Western blot were significantly reduced at 24 h after reperfusion. These results suggest that reductions in expression of Na+-cotransporter genes in the proximal tubules may be important factors in the impairment in Na+-dependent reabsorption of solutes and that decrease in AQP2 protein may be involved in defect in urinary concentration ability in rabbits with ischemic acute renal failure.

Analysis of Variance↗
PubMed2000

Protection against hydrogen peroxide induced injury in renal proximal tubule cell lines by inhibition of poly(ADP-ribose) synthase.

Radicals including superoxide anions, hydrogen peroxide or hydroxyl radicals and NO or peroxynitrite cause the breakage of DNA strands and activation of poly-(ADP-ribose) synthase (PARS). Recent studies showed that inhibition of PARS activity reduces the tissue injury after exposure to oxidative stress. However, the role of PARS in renal injury by oxidants has not been examined. In this study effect of a PARS inhibitor, 3-aminobenamide (3-AB), on injury of opossum kidney or LLC-PK(1) cells by hydrogen peroxide or tert-butyl hydroperoxide (t-BHP) was examined. The exposure of opossum kidney cells to hydrogen peroxide activated PARS and decreased cellular adenosine triphosphate levels in a concentration-dependent manner. Inhibition of PARS with 3-AB prevented the cell death induced by hydrogen peroxide and also prevented adenosine triphosphate depletion. 3-AB did not have hydroxyl radical scavenging effect. In contrast, t-BHP did not affect the PARS activity. The decrease in cellular adenosine triphosphate levels by t-BHP was less than that by hydrogen peroxide. 3-AB failed to prevent the cell death induced by t-BHP. PARS activation after exposure of hydrogen peroxide was inhibited by addition of t-BHP. However, t-BHP showed an additive effect on cell death with hydrogen peroxide. These results indicate that activation of PARS plays an important role in hydrogen peroxide induced injury in opossum kidney cells and that hydrogen peroxide and t-BHP induce cell injury by different mechanisms.

Adenosine Triphosphate↗
PubMed1999

The MCFONTZL classification system for soft-tissue injuries to the face.

A review of the literature and case records reflected a need for the development of a clinically applicable assessment scheme and classification system for soft-tissue laceration injuries to the face. Herein, a systematic approach for assessing facial lacerations is proposed based on location, depth of penetration, branching, directionality, size, presence of soft-tissue defect, and translation of such injuries into the current procedural terminology (CPT) code. Moreover, a new classification system for facial laceration injuries is presented that may serve as the basis for simplification of current billing codes. Prospective clinical application of this classification system may lead to standardization of facial injury assessment and improvement in the incomplete and inconsistent patient record. This system will establish a reliable database that may identify factors in soft-tissue injuries that contribute to poor aesthetic results or secondary functional deformities. These data will lead to the modification of established treatment plans.

Facial Injuries↗
PubMed1999

Enhancement of bistability in spinal motoneurons in vivo by the noradrenergic alpha1 agonist methoxamine.

Enhancement of bistability in spinal motoneurons in vivo by the noradrenergic alpha1 agonist methoxamine. Like many types of motoneurons, spinal motoneurons in the adult mammal can exhibit bistable behavior. This means that short periods of excitatory input can initiate long periods of self-sustained firing and that equally short periods of inhibition can return the cell to the quiescent state. Usually, the presence of one of the monoamines (either serotonin or norepinephrine) is required for spinal motoneurons to express bistable behaviors. Because the decerebrate cat preparation has tonic activity in monoaminergic fibers that originate in the brain stem and project to spinal motoneurons, these cells sometimes exhibit bistable behavior. However, exogenous application of the noradrenergic alpha1 agonist methoxamine greatly enhances bistable behavior in the decerebrate. The goal of this study was to identify the mechanisms of this action of methoxamine. The total persistent inward current (IPIC) in spinal motoneurons in the decerebrate cat was measured from I-V functions generated by triangular voltage commands applied using discontinuous single electrode voltage clamp. The effect of methoxamine on IPIC was assessed by comparing its properties in a control cell sample without methoxamine to its properties in a sample of cells obtained after application of methoxamine. In most experiments, at least one cell was obtained from each sample. Our results showed that methoxamine approximately doubled the amplitude of IPIC without changing its onset voltage, its offset voltage, or its persistence. The reduced amplitude was a consistent finding within experiments and so was unlikely to be caused by interanimal variability. In addition, methoxamine depolarized motoneurons without altering their input conductances, so that a smaller amount of current was required to reach the onset voltage of IPIC. These effects of methoxamine were approximately equal in all cells. As a result of these changes, methoxamine greatly enhanced the tendency for motoneurons to become bistable. It is proposed that the methoxamine-induced increase in the amplitude of IPIC is effective in enhancing the duration of bistable firing because this increase makes IPIC more resistant to the deactivating effects of the afterhyperpolarizations between spikes.

Adrenergic alpha-Agonists↗
PubMed1999

Paradoxical effect of QX-314 on persistent inward currents and bistable behavior in spinal motoneurons in vivo.

Spinal motoneurons can exhibit bistable behavior, which consists of stable self-sustained firing that is initiated by a brief excitatory input and terminated by brief inhibitory input. This bistable behavior is generated by a persistent inward current (I(PIC)). In cat motoneurons with low input conductances and slow axonal conduction velocities, I(PIC) exhibits little decay with time and thus self-sustained firing is long-lasting. In contrast, in cells that have high input conductances and fast conduction velocities, I(PIC) decays with time, and these cells cannot maintain long duration self-sustained firing. An alternative way to measure bistable behavior is to assess plateau potentials after the action potential has been blocked by intracellular injection of QX-314 to block sodium (Na(+)) currents. However, QX-314 also blocks calcium (Ca(2+)) currents and, because I(PIC) may be generated by a mixture of Ca(2+) and Na(+) currents, a reduction in amplitude of I(PIC) was expected. We therefore systematically compared the properties of I(PIC) in a sample of cells recorded with QX-314 to a control sample of cells without QX-314, which was obtained in a previous study. Single-electrode voltage-clamp techniques were applied in spinal motoneurons in the decerebrate cat preparation following administration of a standardized dose of the noradrenergic alpha1 agonist methoxamine. In the sample with QX-314, the average value of I(PIC) was only about half that in the control sample. However, the reduction of I(PIC) was much greater in cells with slow as compared with fast conduction velocities. Because a substantial portion of I(PIC) originates in dendritic regions and because conduction velocity covaries with the extent of the dendritic tree, this result suggests that QX-314 may fail to diffuse very far into the dendrites of the largest motoneurons. The analysis of the decay of I(PIC) and plateau potentials in cells with QX-314 also produced an unexpected result: QX-314 virtually eliminated time-dependent decay in both I(PIC) and plateau potentials. Consequently, I(PIC) became equally persistent in high and low input conductance cells. Therefore the decay in I(PIC) in high input conductance cells in the absence of QX-314 is not due to an intrinsic tendency of the underlying inward current to decay. Instead it is possible that the decay may result from activation of a slow outward current. Overall, these results show that QX-314 has a profound effect on I(PIC) and thus plateau potentials obtained using QX-314 do not accurately reflect the properties of I(PIC) in normal cells without QX-314.

Anesthetics, Local↗