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PubMed1997

[Measurement of receptor-operated Ca2+ influx by microspectrofluometry combined with the whole-cell patch clamp technique].

Signal transduction from mouse bradykinin B2-receptors to Ca2+ influx was studied in single control or v-Ki-ras-transformed NIH/3T3 (DT) fibroblasts. Microspectrofluometry (fura-2) was combined with the whole-cell patch-clamp technique to study bradykinin-activated Ca2+ influx. Cytosolic Ca2+ oscillations observed at holding potentials of -20 to -80 mV were terminated by holding at -10 mV or more depolarized potentials. Bradykinin significantly enhanced the hyperpolarization-induced increases in the intracellular free Ca2+ concentration upon membrane hyperpolarization only in DT cells but not in control cells. Internal application of 10 microM inositol 1,3,4,5-tetrakisphosphate (InsP4) mimicked membrane potential-dependent Ca2+ entry. Activation of B2-receptors resulted in a decrease of cellular fluorescence at the excitation wavelength of 340 or 360 nm after MnCl2 application in DT cells. This Mn2+ entry through the Ca2+ influx pathway increased with membrane hyperpolarization below -20 mV. The results suggest that bradykinin-induced cytosolic Ca2+ oscillations in ras-transformed NIH/3T3 cells are maintained by bradykinin-activated continuous Ca2+ influx, which may use Ins(1,3,4,5)P4 as an intracellular messenger.

Animals↗

PubMed1997

Patch-clamp characterization of secretory process in human basophils.

The effects of the intracellular Ca2+ concentration ([Ca2+]i) and a nonhydrolyzable guanosine triphosphate, guanosine 5'-o-(3-thiotriphosphate) (GTP-gamma-S), on secretion were studied by a patch-clamp technique in human basophils. When 10 microM Ca2+ were applied intracellularly, the granules dispersed rapidly, moved vigorously and fused to the cell membrane in 5 min. When the cells were exposed to 2 microM [Ca2+]i and 100 microM GTP-gamma-S, the granules dispersed gradually and granule fusion continued for 7-10 min. The plasma membrane conductance did not appreciably change with either 10 microM [Ca2+]i alone or 2 microM [Ca2+]i + 100 microM GTP-gamma-S. Intracellular application of Ca2+, 1-10 microM, caused a dose-dependent increase in cell membrane capacitance, which reflects granule membrane fusion, indicating exocytosis in a Ca2+ concentration-dependent manner. The addition of 100 microM GTP-gamma-S promoted an increase in the plasma membrane capacitance at concentrations from 0.1 to 2 microM [Ca2+]i and at 2 microM [Ca2+]i the increase was 4.4 times greater than that with 2 microM [Ca2+]i alone. These results indicate that certain G protein(s) promote Ca2+-dependent exocytosis in human basophils.

Basophils↗

PubMed1996

Patch-clamp detection of neurotransmitters in capillary electrophoresis.

Gamma-aminobutyrate acid, L-glutamate, and N-methyl-D-aspartate were separated by capillary electrophoresis and detected by the use of whole-cell and outside-out patch-clamp techniques on freshly dissociated rat olfactory interneurons. These neuroactive compounds could be identified from their electrophoretic migration times, unitary channel conductances, and power spectra that yielded corner frequencies and mean single-channel conductances characteristic for each of the different agonist-receptor interactions. This technique has the sensitivity to observe the opening of a single ion channel for agonists separated by capillary electrophoresis.

Animals↗

PubMed1997

A patch clamp study of a glutamatergic chloride channel on pharyngeal muscle of the nematode Ascaris suum.

Glutamatergic chloride channels on the pharyngeal muscle of Ascaris suum could be activated with glutamate and ivermectin and reversibly blocked with picrotoxin using the patch clamp technique. No activation was observed with GABA, glycine and acetylcholine. Most of the current was carried by the main subconductance state of 21 pS. Two smaller subconductance states occurred rarely. Open time histograms could be best fitted by two time constants of tau(o1) = 0.33 ms and tau(o2) = 9.8 ms present at all glutamate concentrations applied. The results suggest that some properties of the channel investigated here are different from other glutamatergic chloride channels reported from various animals.

Acetylcholine↗

PubMed2000

Electrophysiological characterization of human keratinocytes using the patch-clamp technique.

The living, not-cornified part of the epidermis consists mainly of keratinocytes. The control mechanisms of proliferation and differentiation are only partly understood. Similarly, the influence of ionic channels of the cell membrane on the proliferation of keratinocytes remains unclear. Preliminary investigations point to a relation between the opening of ionic channels and keratinocyte proliferation. Therefore, voltage clamp experiments were performed to gain further knowledge of the electrophysiological characteristics of human keratinocyte cellular membranes. In-vitro cultured keratinocytes of the cell line HaCaT were characterized by means of the voltage-clamp technique. As measured in the whole-cell configuration, changing the extracellular K+ or Cl--concentration shifted the membrane potential of HaCaT cells. Application of the patch-clamp-technique in the cell-attached and inside-out configuration revealed an ionic channel with a conductance of multiples of 200 pS. The reversal potential of the single channel current was shifted by substituting of intracellular Cl- by aspartate-. Channel openings disappeared after addition of 0.1 mM of the anion channel blocker 4',4' diisothiocyanato-stilbene-2-2' disulfonic acid (DIDS). It is concluded that this channel contributes to the Cl--conductance of the cellular membrane and is a determinant of the membrane potential of human keratinocytes. This channel may represent a target for pharmacological manipulation of the membrane potential and possibly the growth of human keratinocytes in dermatological proliferation disorders.

Cell Division↗

PubMed2006

Firing pattern of rat hippocampal neurons: a perforated patch clamp study.

To test whether the slow afterhyperpolarization (sAHP) underlies the filter function of hippocampal granule cells (GCs), we compared the sAHP and spike frequency adaptation between granule cells and CA3 pyramidal cells (PCs) in hippocampal slices employing gramicidin perforated patch clamp recordings to best preserve the physiological cytoplasmic constitution. sAHPs were evoked in GCs and PCs with trains of action potentials in current clamp mode and showed comparable kinetics in both types of cells. The threshold frequency (500 ms firing) triggering a detectable sAHP was approximately 10 Hz and approximately 3 Hz in GCs and PCs, respectively. Half maximal sAHPs were reached at 30 Hz and 8 Hz in GCs and PCs, respectively. Maximal amplitude of sAHPs in GCs amounted to approximately 3.5 mV, was approximately 2-fold smaller than in PCs and could not be further increased with higher firing frequencies. The time course of sAHP activation was investigated with 50 Hz trains of action potentials applied for increasing durations. In both types of cells, the sAHP amplitude increased with a time constant of approximately 400 ms. Nevertheless, sAHP never exceeded 4 mV in GCs but rose to approximately 12 mV in PCs when cells fired for 3 s. The repetitive firing pattern of GCs and PCs was compared by injecting current amplitudes adjusted to provoke an initial firing frequency of 50 Hz. In GCs firing frequency declined slower (tau = 229 ms) and leveled off at a higher tonic firing frequency (28 Hz) when compared to PCs (tau = 126 ms, 18 Hz). We conclude that the intrinsic excitability of GCs cannot be primarily regulated by the sAHP. The sAHP in GCs is minimal most likely due to a small sAHP-channel density as well as to a more rigid control of intracellular Ca(2+) levels.

Animals↗

PubMed1995

Highly cooperative Ca2+ elevations in response to Ins(1,4,5)P3 microperfusion through a patch-clamp pipette.

To study the initial kinetics of Ins(1,4,5)P3-induced [Ca2+]i elevations with a high time resolution and to avoid the problem of cell-to-cell heterogeneity, we have used the combined patch-clamp/microfluorimetry technique. The mathematical description of the microperfusion of Ins(1,4,5)P3 and the subsequent Ca2+ release consists of a monoexponential decay (cytosolic Ins(1,4,5)P3 concentration) and a Hill equation (Ins(1,4,5)P3 dose-response curve). Two additional Hill equations and an integration were necessary to include a putative dependence of Ins(1,4,5)P3-induced Ca2+ release on [Ca2+]i. Best-fitting analysis assuming [Ca2+]i-independent Ca2+ release yielded Hill coefficients between 4 and 12. The high cooperativity was also observed with the poorly metabolizable analog Ins(2,4,5)P3 and was independent of extracellular [Ca2+]. Best-fitting analysis including a positive [Ca2+]i feedback suggested a cooperativity on the level of Ins(1,4,5)P3-induced channel opening (n = 2) and an enhancement of Ins(1,4,5)P3-induced Ca2+ release by [Ca2+]i. In summary, the onset kinetics of Ins(1,4,5)P3-induced [Ca2+]i elevations in single HL-60 granulocytes showed a very high cooperativity, presumably because of a cooperativity on the level of channel opening and a positive Ca2+ feedback, but not because of Ca2+ influx or Ins(1,4,5)P3 metabolism. This high cooperativity, acting in concert with negative feedback mechanisms, might play an important role in the fine-tuning of the cellular Ca2+ signal.

Calcium↗

PubMed1995

[Characterization of Ca2+ influx in human neutrophils using the patch clamp technique].

In neutrophils, Ca2+ influx across the plasma membrane occurs in response to a variety of agonists. It plays an important role in the regulation of neutrophil function, in particular exocytosis and release of inflammatory mediators. Using the combination of patch clamp and microfluorimetry techniques, we have found the following characteristics of neutrophil Ca2+ influx: (a) neutrophils do not possess voltage-dependent Ca2+ channels; (b) Ca2+ influx is activated by depletion of intracellular Ca2+ stores, either by Ins(1,4,5)P3, or by Ca(2+)-ATPase inhibitors; (c) Ca2+ influx is not activated by [Ca2+]i elevations and not associated with the activation of non-selective cation channels; (d) Ca2+ influx is associated with the activation of a small, voltage-independent current through a highly Ca(2+)-selective conductance. The current was only seen upon depletion of intracellular Ca2+ stores and showed a pharmacological profile similar to the fluorimetrically detected Ca2+ influx.

Calcium↗

PubMed1987

Cell-attached patch clamp measurement of macroscopic rapid inward sodium current in cultured heart cell reaggregates.

A megaohm seal, cell-attached patch clamp technique utilizing plastic suction pipettes for measuring macroscopic rapid inward sodium current (INa) was applied to cell membrane patches 30 to 100 micron2 in area at the periphery of reaggregates of myocardial cells from newborn rats cultured for 3 to 7 days. The reaggregates were composed of about 20 to several thousand of electrically well-coupled cells, the latter forming spheroidal reaggregates with a diameter of maximally 300 microns. This system was shown to guarantee satisfactory voltage-clamp control during ionic current measurements. The time and voltage dependence of the INa recorded during periods of up to 90 min was similar to that observed in single cardiac cell preparations from adult rats. INa inactivation was described by two time constants (tau h1, and tau h2). For maximal INa tau h1 and tau h2 had values of 1.5 +/- 0.25 ms and 8.7 +/- 3.9 ms (n = 4), respectively. The time course for recovery of INa from inactivation at the reaggregate resting potential exhibited also two time constants (tau re1 = 9.8 +/- 3 ms, tau re2 = 193 +/- 50 ms, n = 5). Estimated current density was about 10 pA/micron2. The concentration of tetrodotoxin needed to reduce maximal INa by 75% was 85 times lower in the reaggregates than it was in freshly isolated heart muscle cells from adult rats. The present system offers a combination of features that should make it well-suited for the study of both short- and long-term effects on the sodium channels in neonatal heart cells: Easy handling of the object, great electric stability, high time and amplitude resolution during ionic current measurements, and viability for at least one week.

Animals↗

PubMed2003

Patch-clamp analysis in canine cardiac Purkinje cells of a novel sodium component in the pacemaker range.

A putative Na+ component playing a role in the initiation and maintenance of spontaneous discharge in Purkinje fibres was studied by means of the whole-cell patch-clamp technique in canine cardiac single Purkinje cells. In 4 mM [K+]o, during depolarising clamp steps, a slowly inactivating current appeared at approximately -58 mV, negative to the threshold for the fast Na+ current (INa; approximately -50 mV). During depolarising ramps, the current underwent inward rectification with a negative slope region that began at approximately -60 mV. The current underlying the negative slope increased during faster ramps, decreased as a function of time when the initial depolarising ramp was over, decreased during depolarisations positive to approximately -35 mV and was much larger than the current during the symmetrical repolarising ramp. Increasing biphasic ('oscillatory') voltage ramps required much smaller currents at a holding potential (Vh) of -60 mV than at -80 mV and were associated with a marked decrease in slope conductance. At Vh -50/-40 mV, the oscillatory ramp currents and superimposed pulse currents reversed direction. The negative slope in the I-V relation as well as the change in current direction at -50/-40 mV were markedly reduced by tetrodotoxin (15 microM) and lidocaine (lignocaine, 100 microM) and therefore are due to a slowly inactivating Na+ current, labelled here INa3. Lower [K+]o (2.7 mM) reduced the steady state slope conductance as well as the current in the diastolic range, and increased as well as shifted INa3 in a negative direction. High [K+]o had the opposite effects. Cs+ (2 mM) and Ba2+ (2 mM) reduced the initial current during depolarising ramps but not INa3. In current-clamp mode, current-induced voltage oscillations elicited action potentials through a gradual transition between diastolic depolarisation and upstroke, consistent with the activation of INa3. Thus, the initiation and maintenance of spontaneous discharge in Purkinje strands appear to involve a voltage- and K+-dependent decrease in K+ conductance as well as the activation of a voltage- and time-dependent inward Na+ current (INa3) with slow inactivation kinetics.

Algorithms↗

PubMed1992

Perforated patch-clamp analysis of the passive membrane properties of three classes of hippocampal neurons.

1. Perforated patch-clamp recordings were made from the three major classes of hippocampal neurons in conventional in vitro slices prepared from adult guinea pigs. This technique provided experimental estimates of passive membrane properties (input resistance, RN, and membrane time constant, tau m) determined in the absence of the leak conductance associated with microelectrode impalement or the washout of cytoplasmic constituents associated with conventional whole-cell recordings. 2. To facilitate comparison of our data with previous results and to determine the passive membrane properties under conditions as physiological as possible, recordings were made at the resting potential, in physiological saline, and without any added blockers of voltage-dependent conductances. 3. Membrane-potential responses to current steps were analyzed, and four criteria were used to identify voltage responses that were the least affected by activation of voltage-dependent conductances. tau m was estimated from the slowest component (tau 0) of multiexponential fits of responses deemed passive by these criteria. RN was estimated from the slope of the linear region in the hyperpolarizing direction of the voltage-current relation. 4. It was not possible to measure purely passive membrane properties that were completely independent of membrane potential in any of the three classes of hippocampal neurons. Changing the membrane potential by constant current injection resulted in changes in RN and tau 0; subthreshold depolarization produced an increase, and hyperpolarization a decrease, in both RN and tau 0 for all three classes of hippocampal neurons. 5. Each of the three classes of hippocampal neurons also displayed a depolarizing "sag" during larger hyperpolarizing voltage transients. To evaluate the effect of the conductances underlying this sag on passive membrane properties, 2-5 mM Cs+ was added to the physiological saline. Extracellular Cs+ effectively blocked the sag in all three classes of hippocampal neurons, but the effect of Cs+ on RN, tau 0, and the voltage dependence of these parameters was unique for each class of neurons. 6. CA1 pyramidal neurons had an RN of 104 +/- 10 (SE) M omega and tau 0 of 28 +/- 2 ms at a resting potential of -64 +/- 2 mV (n = 12). RN and tau 0 were larger at more depolarized potentials in these neurons, but the addition of Cs+ to the physiological saline reversed this voltage dependence. 7. CA3 pyramidal neurons had an RN of 135 +/- 8 M omega and tau 0 of 66 +/- 4 ms at a resting potential of -64 +/- 1 mV (n = 14).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1984

The frog interosseal muscle fiber as a new model for patch clamp studies of chemosensitive- and voltage-sensitive ion channels: actions of acetylcholine and batrachotoxin.

The patch clamp technique was used to record the currents flowing through single ion channels in isolated frog muscle fibers. The majority of the acetylcholine (ACh)-activated channels had a conductance of 32 pS, although 20 pS channels were also occasionally observed. Lifetimes of ACh-activated channels increased with the transmembrane potential in the range from - 30 mV to - 105 mV. In these same fibers we also observed channels which were activated by low concentrations of batrachotoxin (BTX; 10 nM). These channels, presumed to be Na channels, had a conductance of 19 pS and opened at potentials at which Na channels would not normally open. A notable feature of these BTX-activated channels was that they opened and closed repeatedly. Therefore, it appears that the toxin, in addition to activating Na channels, also blocks the inactivation process. The physiological properties of these channels reveal significant differences between the ion channels of tissue-cultured and mature tissues.

Acetylcholine↗

PubMed2001

Inhibitors of the Cl-/HCO3- exchanger activate an anion channel with similar features in the epithelial cells of rabbit gallbladder: patch-clamp analysis.

The stilbene- and dipyridamole-sensitive Cl-conductance (GCl), non-additively activated by some inhibitors of the Cl-/HCO3- exchanger (hydrochlorothiazide, phlorizin, phenylglyoxal) after the exchanger inhibition in the apical plasma membrane of rabbit gallbladder epithelium, has been investigated by patch-clamp technique with cell-attached and inside-out configurations. No Cl- channels were observed under basal conditions or after treatment with 2.5 x 10(-4) mol/l 8-Br-cAMP or hydrochlorothiazide (HCTZ) on the cytosolic side. Conversely, with 2.5 x 10(-4) mol/l HCTZ or 2 mmol/l phlorizin in the pipette, a non-rectifying Cl- channel with about 5 pS conductance and 0.3-0.4 voltage-independent open probability was observed; it was inhibited by 10(-4) - 5 x 10(-4) mol/l SITS, 10(-4) mol/l furosemide or 0.6 x 10(-4) mol/l dipyridamole; the effects of HCTZ and phlorizin were not additive. Open probability increased from 0 (after seal formation) to a maximum of 0.3-0.4 reached in 7-9 min. Similar results were obtained with both configurations. With the cell-attached configuration, HCTZ added to the bath did not activate Cl- channels in the patch. The channel was shown to exclude cations, to be selective for Cl-, but also conductive for gluconate (PGluc/PCl = 0.18). On this basis, it is concluded that: (1) GCl, activated either by HCTZ or phlorizin, has the same underlying anion channels, (2) the channels can be activated only on the external side of the membrane, also in the absence of cytoplasm, without cellular mediations or effects at a distance along the membrane, (3) the channels are inhibited by the same drugs which inhibit the very small intrinsic anion conductance of the exchanger, (4) they are either related to a slow conversion of inhibited exchangers into channels or, less probably, they are parallel to the exchanger and slowly activated by intra-membrane (or membrane-bound) mediators in their turn activated by near, inhibited exchangers.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1995

Patch clamp study of histamine activated potassium currents on rabbit olfactory bulb neurons.

Effects of histamine, histamine agonists and antagonists on steady state current in principal neurons and interneurons were investigated in thin slices from the olfactory bulb of newborn rabbits with the nystatin perforated patch-clamp technique and local pipette application. No change in steady state current was observed in mitral cells. In most of the periglomerular, juxtaglomerular and granular cells, however, H1-receptor activation caused an outward current; a similar effect, but mostly not on the same neurons was elicited by 8-bromo-cyclic-AMP. These currents were reversed at the potassium equilibrium potential, indicating block of a potassium current. Specific H3-receptor activation and cyclic GMP were ineffective. Histamine usually caused a combined effect beginning with an inward current. Histaminergic neurons fire with changes in behavioural state and can, by the described mechanisms, markedly influence signal processing in the olfactory bulb.

Animals↗

PubMed1996

Patch-clamp characterization of nicotinic receptors in a subpopulation of lamina X neurones in rat spinal cord slices.

1. Nicotinic acetylcholine receptors (nAChRs) on lamina X neurones in neonate (P1-P12) rat transverse thoracolumbar spinal cord slices were studied using the whole-cell patch-clamp technique. These visually selected neurones are located dorsal to the central canal, mainly in the ventral half of the dorsal commissure. 2. Pressure application of the nicotinic agonist 1,1-dimethyl-4-phenyl-piperazinium (DMPP) (1 mM) induced a rapid depolarization on which action potentials are superimposed. 3. At -50 mV, DMPP (1 mM), pressure ejected for 100 ms, induced a fast inward current with a mean amplitude of -280 pA (n = 28) in 90% of the neurones recorded. Superfusion of tetrodotoxin (TTX), a solution containing 0 Ca(2+)-high Mg2+, CdCl2 or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) did not abolish the DMPP-induced current, which confirmed a direct postsynaptic effect of DMPP on recorded neurones. 3. The current-voltage (I-V) relationship for DMPP-induced current exhibited a reversal potential of 0 mV (NaCl outside, potassium gluconate inside) and a strong inward rectification. 4. The DMPP-induced responses were blocked by mecamylamine, hexamethonium and d-tubocurarine (dTC) but were insensitive to alpha-bungarotoxin and methyllycaconitine (MLA). 5. We conclude that lamina X neurones located dorsally to the central canal possess nicotinic acetylcholine receptors. Activation of these nicotinic receptors results in depolarization and generation of action potentials. These receptors may be involved in the modulation of the somato- and viscerosensory transmission.

Animals↗

PubMed2006

Strengths and limits of Beta distributions as a means of reconstructing the true single-channel current in patch clamp time series with fast gating.

Single-channel current seems to be one of the most obvious characteristics of ion transport. But in some cases, its determination is more complex than anticipated at first glance. Problems arise from fast gating in time series of patch-clamp current, which can lead to a reduced apparent (measured) single-channel current. Reduction is caused by undetected averaging over closed and open intervals in the anti-aliasing filter. Here it is shown that fitting the measured amplitude histograms by Beta distributions is an efficient tool of reconstructing the true current level from measured data. This approach becomes even more powerful when it is applied to amplitude distributions-per-level. Simulated time series are employed to show that the error sum is a good guideline for finding the correct current level. Furthermore, they show that a Markov model smaller than the one used for gating analysis can be used for current determination (mostly O-C, i.e., open-closed). This increases the reliability of the Beta fit. The knowledge of the true current level is not only important for the understanding of the biophysical properties of the channel. It is also a prerequisite for the correct determination of the rate constants of gating. The approach is applied to measured data. The examples reveal the limits of the analysis imposed by the signal-to-noise ratio and the shape of the amplitude distribution. One application shows that the negative slope of the I-V curve of the human MaxiK channel expressed in HEK293 cells is caused by fast gating.

Algorithms↗

PubMed1995

Hebbian induction of LTP in visual cortex: perforated patch-clamp study in cultured neurons.

1. To see whether presynaptic activation paired with postsynaptic depolarization is necessary for the induction of long-term potentiation (LTP) in visual cortex or whether an activation of postsynaptic receptors in conjunction with depolarization is sufficient, we carried out perforated patch-clamp recordings with nystatin from cultured cortical neurons of rats. 2. Recorded neurons were monosynaptically activated either by electrical stimulation of an adjacent neuron or by direct activation of glutamate on "hot spots" of dendrites through iontophoresis or pressure ejection. In experiments in which cultured neurons were stained immunocytochemically with antibody against synaptophysin after electrophysiological recordings, hot spots were found to correspond to probable synaptic sites. 3. Excitatory postsynaptic currents (EPSCs) evoked by test stimulation applied to the adjacent neuron at 0.1 Hz were recorded at a holding potential of -60 or -70 mV for 5-10 min after an establishment of the whole cell recording configuration. Then, stimulation was paired with postsynaptic depolarization (0 mV for 200 ms) at 1 Hz for 30 or 60 s. LTP of EPSCs was induced in 7 of the 15 cells from which stable recordings were obtained for 18-30 min after pairing. 4. When postsynaptic depolarization was paired with direct glutamate application in the absence of presynaptic stimulation in 12 cells, only 1 showed LTP. Postsynaptic depolarization alone did not induce LTP in any of the six cells tested. Also, presynaptic stimulation alone did not induce LTP in any of the five cells tested. 5. These results suggest that the concurrent activation of presynaptic elements with postsynaptic depolarization is necessary for the induction of LTP in visual cortex.

Animals↗

PubMed2000

Admittance-based measurement of membrane capacitance using the EPC-9 patch-clamp amplifier.

A software lock-in amplifier (SLIA) was developed to allow high-time-resolution measurement of membrane capacitance as a single-cell assay of exocytosis. The unique feature of this "virtual instrument" is that it is thoroughly integrated with a computer-controlled patch-clamp amplifier (EPC-9) to allow estimation of equivalent circuit parameters based upon calibrated admittance measurements rather than just relative changes. Since the same software package ("PULSE") controls both the EPC-9 and the SLIA, instrument settings which affect admittance calculations (gain, filtering, etc.) are always "known" by the SLIA. Attenuation and phase shifts introduced within the EPC-9 by low-pass filters and other circuitry are modelled and automatically corrected by the software. In addition, changes in the measured signal introduced by whole-cell capacitance and series resistance compensation are accounted for. The noise of capacitance measurements is nearly optimal and resistive parameters can vary over a large range without inducing artifactual changes in capacitance estimates.

Artifacts↗