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At least 703 records · Page 39Linked to original sources
PubMed2004

Visually guided patch-clamp recording of spinal dorsal horn neuron's postsynaptic current evoked by primary afferent fiber.

The authors describe here the procedures for using the gelatin half-embedding method to obtain thin spinal cord slices with attached dorsal roots and performing visually guided whole-cell patch-clamp recording of postsynaptic currents evoked by primary afferent fibers in rat spinal dorsal horn. A segment of spinal cord with attached dorsal roots was prepared and half-embedded in an agar block with 20% (w/v) gelatin. Thin spinal cord slices with attached dorsal roots were obtained with a vibratome and whole-cell patch-clamp configuration was established under the infrared observation. At the holding potential of -70 mV, spontaneous excitatory postsynaptic currents (EPSCs) and dorsal root stimulation-evoked EPSCs were recorded as inward currents. According to the conduction velocity of afferent fibers and stimulus threshold, evoked EPSCs that are mediated by A-like or C-like fibers were distinguished. At the holding potential of 0 mV, spontaneous inhibitory postsynaptic currents (IPSCs) and dorsal root stimulation-evoked IPSCs were recorded as outward currents. Using 5 micromol/L strychnine or 20 micromol/L bicuculline, GABAergic or glycinergic evoked IPSCs could be isolated. Using visual patch-clamp method synaptic transmission can be accurately assessed by measuring postsynaptic currents of the dorsal horn neurons. More importantly, with the aid of infrared observation, the incidence of failure to establish a clamp configuration can be greatly reduced and it becomes easier to make recordings from the neurons in deep dorsal horn laminae. Thus, the present research approach an effective approach to study the modulation of primary afferent synaptic transmission.

Animals↗
PubMed1992

Euglycemic hyperinsulinemic clamp and oral glucose load in stimulating myocardial glucose utilization during positron emission tomography.

To enable assessment of myocardial viability, myocardial glucose utilization has commonly been stimulated by oral glucose loading. To compare the effects of glucose loading and insulin and glucose infusion (insulin clamp) on PET fluorodeoxyglucose ([18F]FDG) myocardial scan image quality and regional myocardial glucose utilization rate (rMGU), eight patients with angiographically documented coronary artery disease and previous myocardial Q-wave infarction were studied twice, once during insulin clamp and once 1 hr after oral glucose loading. The rMGU rates were derived by graphic Patlak analysis in 33 normal, 10 scar and 6 "hot spot" myocardial segments. Infusion of insulin and glucose gave stable plasma-glucose and serum-insulin levels during imaging. In contrast, glucose loading caused marked changes in plasma-glucose and insulin concentrations. The image quality was clearly superior and the fractional utilization rates of [18F]FDG were twice as high during insulin clamp than after glucose loading (p less than 0.0001). Due to the higher plasma-glucose levels after glucose loading, the calculated rMGU in normal, scar and hot spot myocardial segments was comparable between the two protocols. The insulin clamp technique makes it possible to adjust and maintain a metabolic steady state during the PET study. It does not alter [18F]FDG uptake patterns in different myocardial areas when compared to the standard glucose loading protocol, but this technique results in superior image quality and permits the use of smaller [18F] FDG patient doses.

Administration, Oral↗
PubMed2005

[Advancement of patch-clamp technique and its application in drug high-throughput screening].

The patch-clamp technique, a dominant technique in cellular electrophysiology, is always being regarded as the gold standard for ion channel research. Application of the patch-clamp technique can demonstrate the existences of ion channels and provide valuable information for ion channels, including their electrophysiological properties, molecular structures and the mechanism of drug action. Genomics and proteomics research has showed that the development of drugs for ion channel target would be very promising in future. In recent years, numerous improvements have been achieved, which will facilitate the application of patch clamp technique in drug high-throughput screening. These techniques will break through the bottleneck in the development of drugs aiming at ion channels. New advancements in patch-clamp technique and application in drug high-throughput screening are reviewed in the paper.

Animals↗
PubMed2005

Metabolic stress during hypoglycaemia clamp assessed by microdialysis.

AIM: Microdialysis allows the biochemical analysis of interstitial fluids as a bedside procedure. This technique is of interest to evaluate the glucose dependent metabolism in hypoglycaemic patients. It was the aim to perform subcutaneous and blood microdialysis during hypoglycaemic clamp experiments in 12 healthy young men to reveal basis data for critical care microdialysis practice. METHODS: The hyperinsulinaemic clamp was induced with a continuous infusion of 1.5 mU min(-1) kg(-1) insulin (H-insulin, Hoechst, Frankfurt, Germany). A 20% dextrose solution simultaneously was infused at a variable rate to control blood glucose levels. For hypoglycaemia blood glucose levels were reduced to 40 mg/dL for a 30 min period. Glucose, lactate, pyruvate and glycerol concentrations were semicontinuously measured. RESULTS: The absolute concentrations of glucose and glycerol in blood vs subcutaneous microdialysate were significant different during observation. Until the end of hypoglycaemia, glucose concentration in both compartments declined in parallel, followed by an increase thereafter. During the clamp the subcutaneous glycerol increased threefold, whereas blood glycerol rose with a delay of 15 min and increased only twofold. After the clamp in both compartments glycerol values normalized. The lactate-pyruvate-ratio persisted in normal range throughout the examination. CONCLUSIONS: In our experiment subcutaneous lipolysis increased faster and more profound than blood microdialysis. We propose the microdialysis technique as an additional monitoring tool in hypoglycaemia patients.

Adult↗
PubMed1990

The role of the transcapillary insulin transport in the efficiency of insulin action: studies with glucose clamps and the minimal model.

Insulin action to augment glucose utilization (Rd) and suppress endogenous glucose production is not directly determined by changing plasma insulin, but rather by that insulin which traverses the capillary endothelial boundary to enter the interstitial space bathing insulin-sensitive cells. We have examined the importance of transcapillary insulin transport to the efficiency of insulin action by sampling insulin in thoracic duct lymph, believed to represent interstitial fluid, during euglycemic glucose clamps or intravenous glucose tolerance tests (IVGTTs) in conscious dogs. During clamps (insulin infusion: 0.6 mU/min per kg), we observed a 3:2 gradient between plasma and lymph insulin both at basal and at hyperinsulinemic steady state, which was reestablished after termination of infusion. No such gradient was observed for inulin, a non-metabolizable diffusionary marker infused along with insulin. Furthermore, lymph insulin was proportional to Rd during clamps, and these two independently measured variables were strongly correlated (r = 0.96). These results indicate that transcapillary insulin transport is rate-limiting for insulin action during clamps. Compartmental analysis of insulin and inulin data was consistent with receptor-mediated transport of insulin across capillary endothelium from plasma to interstitium. Glucose tolerance tests were subjected to minimal model analysis, which yields the insulin sensitivity index (SI) and X(t), the rate of net glucose disposition during the intravenous test. Preliminary data reveal a striking similarity between the time courses of X and measured lymph insulin during IVGTTs, evidence that interstitial insulin is virtually at equilibrium with the rate of glucose uptake. Thus, even in the non-steady state, transendothelial insulin transport is the rate determining step for insulin action.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effects of metformin and metoprolol CR on hormones and fibrinolytic variables during a hyperinsulinemic, euglycemic clamp in man.

The aim of this study was to characterize the acute effect of euglycemic (glucose 5.2 +/- 0.6 mmol/l) hyperinsulinemia (mean 118 +/- 32 mU/l) on fibrinolytic variables, free fatty acids (FFA) and counterregulatory hormones. In addition, the effect of chronic treatment with metformin, an oral antidiabetic agent which enhances insulin action, and metoprolol CR, a relatively beta 1-selective adrenergic antagonist, was also evaluated. A randomized, double-blind, placebo-controlled, cross-over study including 18 non-obese men, aged 53 +/- 6 years, was performed. The investigations were performed after each treatment period of 6 weeks in both the postabsorptive state and during a euglycemic, hyperinsulinemic clamp. Compared to the postabsorptive state, plasminogen activator inhibitor (PAI-1) activity and antigen, tissue plasminogen activator (t-PA) antigen and FFA decreased (p < 0.001) after 120 min of euglycemic hyperinsulinemia. In addition, t-PA activity increased (p < 0.01) while blood levels of lipoprotein (a), catecholamines and cortisol remained unchanged. Growth hormone increased during the clamps and this was most pronounced after treatment with metoprolol CR. When the effect of treatment was compared, postabsorptive levels of C-peptide, FFA and t-PA antigen were lower after metformin than after the placebo period (p < 0.05). t-PA antigen also remained lower during the clamp after metformin treatment. No significant effects of metformin or metoprolol CR were seen on insulin-stimulated glucose uptake during the clamps or on postabsorptive levels of counterregulatory hormones, PAI-1 or Lp(a).(ABSTRACT TRUNCATED AT 250 WORDS)

Cross-Over Studies↗
PubMed1996

The role of K+ currents in frequency-dependent spike broadening in Aplysia R20 neurons: a dynamic-clamp analysis.

The R20 neurons of Aplysia exhibit frequency-dependent spike broadening. Previously, we had used two-electrode voltage clamp to examine the mechanisms of this spike broadening (Ma and Koester, 1995). We identified three K+ currents that mediate action-potential repolarization: a transient A-type K+ current (I(Adepol)), a delayed rectifier current (IK-V), and a Ca(2+)-sensitive K+ current(IK-CA). A major constraint in that study was the lack of completely selective blockers for I(Adepol) and I(K-V), resulting in an inability to assess directly the effects of their activation and inactivation on spike broadening. In the present study, the dynamic-clamp technique, which employs computer simulation to inject biologically realistic currents into a cell under current-clamp conditions (Sharp et al., 1993a,b), was used either to block I(Adepol) or I(K-V) or to modify their inactivation properties. The data in this paper, together with earlier results, lead to the following hypothesis for the mechanism of spike broadening in the R20 cells. As the spike train progresses, the primary responsibility for spike repolarization gradually shifts from I(Adepol) to I(K-V) to I(K-Ca). This sequence can be explained on the basis of the relative rates of activation and inactivation of each current with respect to the constantly changing spike durations, the cumulative inactivation of I(Adepol) and I(K-V), and the progressive potentiation of I(K-Ca). Positive feedback interactions between spike broadening and inactivation contribute to the cumulative inactivation of both I(Adepol) and I(K-V). The data also illustrate that when two or more currents have similar driving forces and partially overlapping activation characteristics, selectively blocking one current under current-clamp conditions can lead to a significant underestimate of its normal physiological importance.

Action Potentials↗
PubMed1996

Voltage-clamp analysis of neurons within deep layers of the brain.

Single electrode whole cell current- and voltage-clamp techniques in conjunction with intra- and extracellular phoresis and extracellular application of pharmacological agents were applied to study neurons in deep layers of the brainstem of anesthetized, paralyzed and artificially ventilated cats. We compared slow rhythmic changes and stimulus-evoked postsynaptic current and voltage responses of neurons as they were recorded with fine-tipped microelectrodes filled with 2-3 M 'microelectrode solutions' or with 0.3 M 'patch solutions', or with patch electrodes. The experimental data were then compared with the effects of somatic and dendritic conductance changes simulated in a cell model. A new method was introduced for alternating current and voltage-clamp measurements performed at 300 Hz, which provided quasi-simultaneous measurements of slow changes of spontaneous synaptic currents and potentials. During current or voltage clamp, chemicals which affect voltage- and receptor-controlled conductances were ionophoresed intracellularly through single or theta-type glass electrodes. We show examples of activation of low-voltage activated Ca2+ responses after blockade of Na+ currents by intracellular QX 314 and K+ currents by intracellular Cs+ injections in addition to Sp-cAMPs to activate protein kinase A. TEA, NMDA and GABA were used to demonstrate the effectiveness of extracellular application of drugs through multibarrel electrodes or local application through a 'bath'. The various tests demonstrated that single electrode whole cell current- and voltage-clamp methods, in combination with various techniques for drug application, can be well applied to study the biophysical properties and pharmacological sensitivities of neurons embedded in in vivo networks within deep layers of the brain.

Amplifiers, Electronic↗
PubMed1984

Abdominal aortic cross-clamping. Metabolic and hemodynamic consequences.

We address the question of whether an oxygen debt develops during a period of abdominal aortic cross-clamping that may explain observed hemodynamic changes. Group 1 received morphine sulfate (1 mg/kg) during induction of anesthesia. Group 2 received same dose of morphine sulfate. Group 3 received 4 mg/kg of morphine sulfate. We measured the oxygen consumption (VO2) and the carbon dioxide production levels (VCO2), as well as hemodynamic and biochemical parameters. In groups 1 and 3, VO2 and VCO2 decreased 10% to 13% following abdominal aortic cross-clamping compared with values measured before cross-clamping. In group 2, VO2 and VCO2 decreased 3% and 7%, respectively. On unclamping, the greatest increase in VO2 was observed in group 3 (26%), while in groups 1 and 2, VO2 rose 18% and 5%, respectively. In all three groups, metabolic changes were not paralleled by hemodynamic or temperature changes. Results indicate that oxygen debt developed during abdominal aortic cross-clamping, but this has no effect on hemodynamic changes seen after unclamping. Higher dosage of narcotic administered during anesthetic induction did not temper increase in metabolic rate observed after unclamping.

Aged↗
PubMed1992

Angiotensin and adrenoceptors in the hemodynamic response to aortic cross-clamping.

This study was designed to test the hypothesis that activation of adrenoceptors and/or the renin-angiotensin system plays an important role in the overall hemodynamic response to aortic cross-clamping. The experiments were performed on anesthetized rats pretreated with either saline (control group), an angiotensin-converting enzyme inhibitor (enalapril maleate, 2 mg/kg), an alpha 1-adrenergic antagonist (prazosin hydrochloride, 0.5 mg/kg), a beta-adrenergic antagonist (propranolol hydrochloride, 5 mg/kg), or an alpha 2-adrenergic antagonist (atipamezole, 5 mg/kg). Cross-clamping of the thoracic aorta was associated with an expected increase in mean arterial pressure and systemic vascular resistance in all animals. During the period of cross-clamping, cardiac output gradually decreased in all groups. Animals pretreated with the alpha 1-adrenergic antagonist or the angiotensin-converting enzyme inhibitor developed hypertension of a lesser degree than the control animals, while rats pretreated with the beta-adrenergic or alpha 2-adrenergic antagonist demonstrated a greater arterial hypertension than the control animals. The possible mechanisms underlying the observed differences are discussed. In conclusion, the present study confirms the posed hypothesis that the reninangiotensin and sympathetic nervous systems play an important role in hemodynamic response to cross-clamping of the thoracic aorta.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Single dose cefazolin prophylaxis for postcesarean infections: before vs. after cord clamping.

The objective of this study was to test the hypothesis that 1 g of cefazolin administered preoperatively is no more effective than the same dose administered after cord clamping in preventing postcesarean infectious morbidity. Ninety consecutive laboring subjects undergoing cesarean delivery at > or = 37 weeks gestation were randomized by computer to receive 1 g of cefazolin intravenously preoperatively or after cord clamping in a double-blinded, placebo-controlled study. The 2 groups were compared for differences in maternal and neonatal demographics, and intrapartum and operative characteristics associated with postcesarean infection. Primary maternal outcome variables were endometritis or wound infection. Secondary outcomes included intra-abdominal abscess formation, septic pelvic thrombophlebitis, pneumonia, or urinary tract infection. Neonatal outcomes included sepsis screens, sepsis, pneumonia, and meningitis. Subjects were followed 6 weeks postoperatively for late complications. Subjects receiving cefazolin preoperatively or after cord clamping had similar maternal and neonatal demographics, and intrapartum and operative characteristics. One patient in the former group experienced both endometritis and wound infection. In the latter group, 2 wound infections and 1 case of endometritis occurred (P = 0.35). There were no secondary maternal infections. Two infants treated for pneumonia and 2 other infants readmitted with febrile illnesses were born to mothers receiving cefazolin preoperatively. Overall, 8 neonates were evaluated for suspected sepsis and all had negative studies. Six of these infants' mothers received cefazolin preoperatively (P = 0.28). In conclusion, 1 gram of cefazolin preoperatively is no more effective than the same dose administered after cord clamping in preventing postcesarean infectious morbidity, but is associated with a trend toward increased suspected sepsis in the newborn. However, this trend may be related to differences between the study groups' risk factors for infection.

Bacterial Infections↗
PubMed2004

Peptide nucleic acid clamp PCR: a novel K-ras mutation detection assay for colorectal cancer micrometastases in lymph nodes.

Inaccurate staging of colorectal cancer (CRC) has been attributed to the failure to detect lymph node metastases by conventional pathology. We have previously reported the use of lymphatic mapping to accurately identify those lymph nodes most likely to harbor micrometastatic disease and permit focused pathologic examination. Mutation of K-ras allele at codons 12 or 13 occurs frequently in early stages of CRC development. The purpose of our study was to assess sentinel lymph nodes (SLN) for occult CRC micrometastases using a unique peptide nucleic acid (PNA) clamp PCR assay specific for K-ras mutations. Seventy-two paraffin-embedded primary CRC and paired SLN were evaluated by PNA clamp PCR for K-ras mutations. Thirty primary tumors (42%) were positive for K-ras mutations, and in 5 of these cases the SLN were positive for metastases by Hematoxylin and Eosin staining. PNA clamp PCR identified occult metastases in an additional 6 patients, upstaging 24% of K-ras positive primary CRCs (p = 0.014). No K-ras mutations were detected among the 20 noncancer lymph nodes assessed. This study demonstrates the utility, specificity and sensitivity of PNA clamp PCR assay in identifying occult micrometastases in the SLN of CRC patients by single-base mutation analysis.

Adult↗
PubMed1995

Prevention of obesity in middle-aged monkeys: food intake during body weight clamp.

Prevention of obesity and increase in longevity in obesity-prone rodents can be achieved by long-term moderate dietary restriction. In order to examine the likelihood that caloric restriction could have similar salutary effects in humans, rhesus monkeys, after reaching mature adult stature, were placed on a protocol to clamp or stabilize body weight by weekly caloric adjustment. Furtherweight gain was prevented by this caloric titration procedure, and thus middle-age onset obesity, which is very common in this species, was prevented. The present study analyzed daily food intake for six weight-clamped monkeys and six ad libitum fed age-matched animals over a 3-year period, ages 18.5 to 21.5 years. After approximately 9 years of caloric restriction the daily calorie load to maintain stable adult body weight proved to be 40% less than the amount ingested by ad libitum fed animals. Calories per kg body weight did not differ significantly between the groups although the ad libitum fed animals were significantly fatter than the weight-clamped group. Prevention of obesity using this weight clamp protocol has also maintained lower insulin levels and higher glucose tolerance in the restricted animals.

Age Factors↗
PubMed1987

The influence of sex steroid hormones on plasma calcitonin response to the calcium clamp in normal subjects.

The influence of sex steroid hormones on plasma calcitonin levels in healthy subjects was studied in 15 males and 10 premenopausal (PREMF) and 12 postmenopausal females (PMF). A standardized ionized calcium stimulus was achieved by means of the calcium clamp technique, and a sensitive RIA was used to determine immunoreactive CT (iCT) in plasma. Plasma iCT levels increased in response to the calcium clamp with an initial peak at 15 or 30 min. The iCT levels then declined but remained at an elevated level for the rest of the 180-min infusion period in all three groups. In males a positive correlation was found between the serum testosterone levels at 0 min and the estimates for initial iCT response, i.e., the change between 0 and 15 min (r = 0.80, n = 11, p less than 0.01), between 0 and 30 min (r = 0.56, n = 15, p less than 0.05) and between 0 and the maximum value (r = 0.68, n = 15, p less than 0.01). In the two female groups no such correlation was found. Serum 17 beta-estradiol or dehydroepiandrosterone sulfate concentrations were not correlated either to basal iCT levels or to the iCT response to the calcium clamp. PMF had lower levels of 17 beta-estradiol than PREMF (p less than 0.001), while the testosterone levels were similar. The iCT levels and response to the calcium clamp showed no significant difference in the two groups. The results indicate that sex difference in the plasma CT levels may be related to different testosterone levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2004

Ischemic preconditioning and intermittent clamping improve murine hepatic microcirculation and Kupffer cell function after ischemic injury.

The aim of this study was to evaluate whether the protective effect of intermittent clamping and ischemic preconditioning is related to an improved hepatic microcirculation after ischemia/reperfusion injury. Male C57BL/6 mice were subjected to 75 or 120 min of hepatic ischemia and 1 or 3 hours of reperfusion. The effects of continuous ischemia, intermittent clamping, and ischemic preconditioning before prolonged ischemia on sinusoidal perfusion, leukocyte-endothelial interactions, and Kupffer cell phagocytic activity were analyzed by intravital fluorescence microscopy. Kupffer cell activation was measured by tissue levels of tumor necrosis factor (TNF)-alpha, and the integrity of sinusoidal endothelial cells and Kupffer cells were evaluated by electron microscopy. Continuous ischemia resulted in decreased sinusoidal perfusion rate and phagocytic activity of Kupffer cell, increased leukocyte-endothelial interactions and TNF-alpha levels. Both protective strategies improved sinusoidal perfusion, leukocyte-endothelial interactions and phagocytic activity of Kupffer cells after 75-minutes of ischemia, and intermittent clamping also after 120 minutes ischemia. TNF-alpha release was significantly reduced and sinusoidal wall integrity was preserved by both protective procedures. In conclusion, both strategies are protective against ischemia/reperfusion injury by maintaining hepatic microcirculation and decreasing Kupffer cell activation for clinically relevant ischemic periods, and intermittent clamping appears superior for prolonged ischemia.

Animals↗
PubMed1985

New disposable microvascular clamp.

A new design for a plastic microvascular clamp is described. The clamp consists of two flat blades, with eyes permitting application and removal of the clamp with cross-forceps. Closure is effected by the elasticity of a rubber ring placed around the blades, obviating the need for an articular joint or a spring mechanism. The new design simplifies production of the clamp, which is intended to be disposable, i.e., for once-only use.

Animals↗
PubMed1975

Voltage clamping with a single microelectrode.

A technique is described which allows neurons to be voltage clamped with a single microelectrode, and the advantages of this circuit with respect to conventional bridge techniques are discussed. In this circuit, the single microelectrode is rapidly switched from a current passing to a recording mode. The circuitry consists of: (1) an electronic switch; (2) a high impedance, ultralow input capacity amplifier; (3) a sample-and-hold module; (4) conventional voltage clamping circuitry. The closed electronic switch allows current to flow through the electrode. The switch then opens, and the electrode is in a recording mode. The low input capacity of the preamplifier allows the artifact from the current pulse to rapidly abate, after which time the circuit samples the membrane potential. This cycle is repeated at rates up to 10 kHz. The voltage clamping amplifier senses the output of the sample-and-hold module and adjusts the current pulse amplitude to maintain the desired membrane potential. The system was evaluated in Aplysia neurons by inserting two microelectrodes into a cell. One electrode was used to clamp the cell and the other to independently monitor membrane potential at a remote location in the soma.

Animals↗
PubMed1994

Modeling a non-inactivating delayed rectifier cardiac current using voltage clamp data.

This paper describes a new parameter estimation method applicable to experimental voltage-clamp records. The method is based on the Hodgkin-Huxley (HH) representation of a generic non-inactivating delayed rectifier current (IK) which can be assimilated to the delayed rectifier potassium current of cardiac cells. The model involves a single gating variable of activation (chi) of degree (lambda chi). Its parameters include the voltage-dependent steady-state characteristic (chi infinity), time constant tau chi, the degree lambda chi as a positive integer, and the maximal conductance gK. The method is based on linear optimization. It implements a series of least-squares minimization steps to calculate a first estimate of each model parameter, followed by global minimization to obtain final estimates. The required data, in the form of ionic current responses, correspond to standard voltage-clamp protocols. The effects of noise are minimized by avoiding the use of the time derivative of IK in the calculations. Simulated voltage-clamp data using either a HH model or a five-state Markov chain (MC) model served two purposes: (i) to test the performance of the HH parameter estimation method, and (ii) to study the suitability of the HH model to reproduce data generated by models other than HH. A nominal MC model was obtained by fitting its current responses to those of the HH model. Rate constants of the nominal MC model were then modified and voltage-clamp current responses were generated. Excellent results were obtained with HH and nominal MC data. Data sets generated by a 20% change in the rate constants of the nominal MC model showed that the closed-state rate constants have only a limited influence on the HH parameter estimates, whereas changes in the closed-to-open rate constants produce substantial effects. Nevertheless, a given MC data set can be fitted quite closely by a HH model. In the light of these simulation results it is indicated that an hybrid HH-MC representation of IK data would be more flexible than a straight HH model by removing some of the constraints between the rate constants, and less cumbersome than a straight MC model by substantially reducing the number of parameters to be estimated.

Electrophysiology↗