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PubMed2006

Capacitive-loaded interstitial antennas for perfect matching and desirable SAR distributions.

New interstitial antennas are proposed. They basically consist of coaxial cable and two types of capacitive loads. One is tipped at the end of antennas, which helps almost perfect matching possible. The others are located in the middle and needed for better specific absorption rate (SAR) distribution. To distinguish them, one at the end is called the end-capacitive load (ECL) and the others in the middle the middle-capacitive loads (MCLs). Depending on the number of the MCLs, ZMIA (zero MCL interstitial antenna), OMIA (one MCL interstitial antenna) and two MCL interstitial antenna (TMIA) are named and a matching technique based on transmission line theory is suggested. To verify the technique, the three antennas immersed in muscle phantom are designed, fabricated, measured and compared. The measured reflection coefficients of ZMIA, OMIA, and TMIA are -28.4, -21.9, and -22.8 dB, respectively, one of which, -28.4 dB may be considered as the best among those reported. The compared results show that the measured ones are in good agreement with the calculated (predicted) ones. The three antennas are also measured for the SAR distributions. The measured results indicate that the TMIA has the best performance as expected and the region more than 43 degrees C is a rugby ball (major axis 6 cm and minor axis 2.9 cm) with only one TMIA, which confirms that they may be used for the treatment for big-sized and deep-seated tumor or cancer.

Computer Simulation↗
PubMed2005

Evaluation of a new annular capacitance probe for biomass monitoring in industrial pilot-scale fermentations.

The four-pin electrode capacitance probe has already shown to be a valuable tool for on-line monitoring viable biomass concentration in industrial-type fermentations. A new prototype annular probe was developed and its performance in real-time monitoring the concentration of viable cells during industrial pilot-scale fermentation for the production of an Active Pharmaceutical Ingredient (API) was investigated and compared to the four-pin probe. A set of 14 fermentations was monitored on-line: four of them with the four-pin probe, the remaining with the annular probe. The performance of both the annular and the four-pin electrode probe were compared against each other and against off-line measurements (viscosity and packed mycelial volume). The prototype annular probe showed to have higher signal intensity and sensitivity than the standard four-pin probe, with higher signal-to-noise ratio. Furthermore, its new design and construction proved to be easier to handle in an industrial environment.

Bioreactors↗
PubMed2003

Calcium influx induced by activation of receptor tyrosine kinases in SV40-transfected human corneal endothelial cells.

This study was undertaken to investigate electrophysiological properties of immortalized SV40-transfected human corneal endothelial cells (HCEC-SV40) combined with the analysis of intracellular Ca(2+) responses mediated by ligands for receptor tyrosine kinases (RTK). In addition, the effects of several tyrosine kinase inhibitors were tested on Ca(2+) inflow mediated by induction of capacitative calcium entry (CCE). Patch-clamp techniques and measurements of the intracellular free Ca(2+) ([Ca(2+)](i)) by fura-2 were performed using HCEC-SV40. Stimulation of fibroblast growth factor receptors (FGFR) (e.g. by basic-FGF) (10 ng ml(-1)) elicited activation of Ca(2+) permeable channels and a subsequent increase of cytosolic free Ca(2+) in HCEC-SV40. This effect could be disrupted by the L-type Ca(2+) channel blocker nifedipine (5 microM). In addition, nifedipine significantly reduced the magnitude of CCE. Inhibition of protein tyrosine kinases (PTKs) by genistein, lavendustin A, or tyrphostin 51 (all 5 microM) also led to a reduction of CCE in HCEC-SV40. This study demonstrates for the first time that L-type Ca(2+) channel activity in HCEC-SV40 is linked to the activity of FGF receptor tyrosine kinases. These data regarding Ca(2+) inflow through Ca(2+) channels could be useful for investigation of culture and vitality conditions of HCEC.

Calcium↗
PubMed2002

Increase in cellular glutamate levels stimulates exocytosis in pancreatic beta-cells.

Glutamate has been implicated as an intracellular messenger in the regulation of insulin secretion in response to glucose. Here we demonstrate by measurements of cell capacitance in rat pancreatic beta-cells that glutamate (1 mM) enhanced Ca2+-dependent exocytosis. Glutamate (1 mM) also stimulated insulin secretion from permeabilized rat beta-cells. The effect was dose-dependent (half-maximum at 5.1 mM) and maximal at 10 mM glutamate. Glutamate-induced exocytosis was stronger in rat beta-cells and clonal INS-1E cells compared to beta-cells isolated from mice and in parental INS-1 cells, which correlated with the expressed levels of glutamate dehydrogenase. Glutamate-induced exocytosis was inhibited by the protonophores FCCP and SF6847, by the vacuolar-type H+-ATPase inhibitor bafilomycin A(1) and by the glutamate transport inhibitor Evans Blue. Our data provide evidence that exocytosis in beta-cells can be modulated by physiological increases in cellular glutamate levels. The results suggest that stimulation of exocytosis is associated with accumulation of glutamate in the secretory granules, a process that is dependent on the transgranular proton gradient.

Animals↗
PubMed2005

Dynamic analysis of capacitive micromachined ultrasonic transducers.

Electrostatic transducers are usually operated under a DC bias below their collapse voltage. The same scheme has been adopted for capacitive micromachined ultrasonic transducers (cMUTs). DC bias deflects the cMUT membranes toward the substrate, so that their centers are free to move during both receive and transmit operations. In this paper, we present time-domain, finite element calculations for cMUTs using LS-DYNA, a commercially available finite element package. In addition to this DC bias mode, other new cMUT operations (collapse and collapse-snapback) have recently been demonstrated. Because cMUT membranes make contact with the substrate in these new operations, modeling of these cMUTs should include contact analysis. Our model was a cMUT transducer consisting of many hexagonal membranes; because it was symmetrical, we modeled only one-sixth of a hexagonal cell loaded with a fluid medium. The finite element results for both conventional and collapse modes were compared to measurements made by an optical interferometer; a good match was observed. Thus, the model is useful for designing cMUTs that operate in regimes where membranes make contact with the substrate.

Computer Simulation↗
PubMed2004

Enlargeosome, an exocytic vesicle resistant to nonionic detergents, undergoes endocytosis via a nonacidic route.

Enlargeosomes, a new type of widely expressed cytoplasmic vesicles, undergo tetanus toxin-insensitive exocytosis in response to cytosolic Ca(2+) concentration ([Ca(2+)](i)) rises. Cell biology of enlargeosomes is still largely unknown. By combining immunocytochemistry (marker desmoyokin-Ahnak, d/A) to capacitance electrophysiology in the enlargeosome-rich, neurosecretion-defective clone PC12-27, we show that 1) the two responses, cell surface enlargement and d/A surface appearance, occur with similar kinetics and in the same low micromolar [Ca(2+)](i) range, no matter whether induced by photolysis of the caged Ca(2+) compound o-nitrophenyl EGTA or by the Ca(2+) ionophore ionomycin. Thus, enlargeosomes seem to account, at least in large part, for the exocytic processes triggered by the two stimulations. 2. The enlargeosome membranes are resistant to nonionic detergents but distinct from other resistant membranes, rich in caveolin, Thy1, and/or flotillin1. 3. Cell cholesterol depletion, which affects many membrane fusions, neither disrupts enlargeosomes nor affects their regulated exocytosis. 4. The postexocytic cell surface decline is [Ca(2+)](i) dependent. 5. Exocytized d/A-rich membranes are endocytized and trafficked along an intracellular pathway by nonacidic organelles, distinct from classical endosomes and lysosomes. Our data define specific aspects of enlargeosomes and suggest their participation, in addition to cell differentiation and repair, for which evidence already exists, to other physiological and pathological processes.

Animals↗
PubMed2003

Investigation of Na(+),K(+)-ATPase on a solid supported membrane: the role of acylphosphatase on the ion transport mechanism.

Charge translocation by Na(+),K(+)-ATPase was investigated by adsorbing membrane fragments containing Na(+),K(+)-ATPase from pig kidney on a solid supported membrane (SSM). Upon adsorption, the ion pumps were activated by performing ATP concentration jumps at the surface of the SSM, and the capacitive current transients generated by Na(+),K(+)-ATPase were measured under potentiostatic conditions. To study the behavior of the ion pump under multiple turnover conditions, ATP concentration jump experiments were carried out in the presence of Na(+) and K(+) ions. Current transients induced by ATP concentration jumps were also recorded in the presence of the enzyme alpha-chymotrypsin. The effect of acylphosphatase (AcP), a cytosolic enzyme that may affect the functioning of Na(+),K(+)-ATPase by hydrolyzing its acylphosphorylated intermediate, was investigated by performing ATP concentration jumps both in the presence and in the absence of AcP. In the presence of Na(+) but not of K(+), the addition of AcP causes the charge translocated as a consequence of ATP concentration jumps to decrease by about 50% over the pH range from 6 to 7, and to increase by about 20% at pH 8. Conversely, no appreciable effect of pH upon the translocated charge is observed in the absence of AcP. The above behavior suggests that protons are involved in the AcP-catalyzed dephosphorylation of the acylphosphorylated intermediate of Na(+),K(+)-ATPase.

Acid Anhydride Hydrolases↗
PubMed2005

Alpha-latrotoxin modulates the secretory machinery via receptor-mediated activation of protein kinase C.

The hypothesis whether alpha-latrotoxin (LTX) could directly regulate the secretory machinery was tested in pancreatic beta cells using combined techniques of membrane capacitance (Cm) measurement and Ca2+ uncaging. Employing ramp increase in [Ca2+]i to stimulate exocytosis, we found that LTX lowers the Ca2+ threshold required for exocytosis without affecting the size of the readily releasable pool (RRP). The burst component of exocytosis in response to step-like [Ca2+]i increase generated by flash photolysis of caged Ca2+ was also speeded up by LTX treatment. LTX increased the maximum rate of exocytosis compared with control responses with similar postflash [Ca2+]i and shifted the Ca2+ dependence of the exocytotic machinery toward lower Ca2+ concentrations. LTXN4C, a LTX mutant which cannot form membrane pores or penetrate through the plasma membrane but has similar affinity for the receptors as the wild-type LTX, mimicked the effect of LTX. Moreover, the effects of both LTX and LTXN4C) were independent of intracellular or extracellular Ca2+ but required extracellular Mg2+. Our data propose that LTX, by binding to the membrane receptors, sensitizes the fusion machinery to Ca2+ and, hence, may permit release at low [Ca2+]i level. This sensitization is mediated by activation of protein kinase C.

Animals↗
PubMed2004

Capacitive coupling: a comparison of measurements in four uterine resectoscopes.

STUDY OBJECTIVE: To compare electrosurgical waveform and electrode integrity as variables in the capacitive induction of current to the external sheath of four different resectoscopes. DESIGN: Laboratory comparative study. SETTING: Surgical laboratory. INSTRUMENTATION: Valleylab Force FX and Force 4 radiofrequency (RF) electrosurgical units (ESUs); resectoscopes from four manufacturers; and rollerball electrodes, both intact and with standardized insulation defects. The ESU was fired over a working range of high- and low-voltage outputs in open circuit conditions, and current and wattage were measured and recorded from both the electrodes and the external sheath. MEASUREMENTS AND MAIN RESULTS: With intact insulation, relatively little current was measurable on the external sheath of any of the resectoscopes regardless of the power or waveform. However, with high-voltage outputs, most proximal insulation defects, and some distal defects, a large proportion of ESU output was measured on the external sheath. There were no such findings with any resectoscope, at any power setting or with any insulation defect, with low-voltage ("cutting") outputs. CONCLUSIONS: These results confirm that high-voltage outputs may present a greater risk for current diversion to the external sheath of any of the monopolar resectoscopes tested and that this could contribute to the risk of lower genital tract injury during RF resectoscopic surgery.

Electric Capacitance↗
PubMed2005

Gastric ulcers evoke hyperexcitability and enhance P2X receptor function in rat gastric sensory neurons.

Tissue inflammation contributes to the development of hyperalgesia, which is at least in part due to altered properties of primary afferent neurons. We hypothesized that gastric ulcers enhance the excitability of gastric sensory neurons and increase their response to purinergic agonists. The rat stomach was surgically exposed, and a retrograde tracer [1.1'-dioctadecyl-3,3,3,'3-tetramethylindocarbocyanine methanesulfonate (DiI)] was injected into the wall of the distal stomach. Kissing ulcers (KUs) were produced by a single injection of acetic acid (0.1 ml for 45 s; 60%) into the clamped gastric lumen. Saline injection served as control. Gastric nodose ganglion (NG) or dorsal root ganglion (DRG) cells were harvested 7 days later and acutely dissociated for whole cell recordings. Based on whole cell capacitance, gastric DRG neurons exhibited larger cell size than NG neurons. Significantly more control gastric DRG neurons compared with NG counterparts had TTX-resistant action potentials. Almost all control NG neurons (90%) compared with significantly less DRG neurons (< or =38%) responded to ATP or alpha,beta-metATP. Whereas none of the control cells exhibited spontaneous activity, about 20% of the neurons from KU animals generated spontaneous action potentials. KUs enhanced excitability as shown by a decrease in threshold for action potential generation, which was in part due to an increased input resistance. This was associated with an increase in the fraction of neurons with TTX-resistant action potentials and cells responding to capsaicin and purinergic agonists. KU doubled the current density evoked by the P2X receptor agonist alpha,beta-metATP and slowed decay of the slowly desensitizing component of the current without affecting the concentration dependence of the response. These data show that KU sensitizes vagal and spinal gastric afferents by affecting both voltage- and ligand-gated channels, thereby potentially contributing to the development of dyspeptic symptoms.

Acetic Acid↗
PubMed2005

CMUT array modeling through free acoustic CMUT modes and analysis of the fluid CMUT interface through Fourier transform methods.

A method for analyzing capacitive micromachined ultrasonic transducer (CMUT) arrays and arrays of elements composed of several CMUTs is proposed. It is based on a combination of a free acoustic mode description of an isolated CMUT, and the coupling of these modes to the fluid in which waves should be excited or detected through an impedance matrix that will depend on frequency. The parameters of the model describing the isolated CMUT is independent of frequency and excitation of neighbor CMUTs, whereas the acoustic impedance matrix describing the coupling to the fluid will depend on both the excitation of neighbor CMUTs and frequency. Hence, this splitting of the calculations has a potential for saving computer time. The analysis gives transfer functions from excitations that vary harmonically with time and space along the array surface to CMUT parameters as current, mode excitations, or output acoustic pressure. Based on this, the response of essentially arbitrary excitations of the CMUTs may be obtained. The method is used to analyze an infinitely large array of circular CMUTs on a rectangular grid. The CMUTs are assumed to be operating in collapsed mode. Sharp resonances are shown to occur that could be significantly damped by adding series resistors to the CMUTs or increasing the water viscosity.

Acoustics↗
PubMed2003

Na/Ca exchange and Na/K-ATPase function are equally concentrated in transverse tubules of rat ventricular myocytes.

Formamide-induced detubulation of rat ventricular myocytes was used to investigate the functional distribution of the Na/Ca exchanger (NCX) and Na/K-ATPase between the t-tubules and external sarcolemma. Detubulation resulted in a 32% decrease in cell capacitance, whereas cell volume was unchanged. Thus, the surface-to-volume ratio was used to assess the success of detubulation. NCX current (I(NCX)) and Na/K pump current (I(pump)) were recorded using whole-cell patch clamp, as Cd-sensitive and K-activated currents, respectively. Both inward and outward I(NCX) density was significantly reduced by approximately 40% in detubulated cells. I(NCX) density at 0 mV decreased from 0.19 +/- 0.03 to 0.10 +/- 0.03 pA/pF upon detubulation. I(pump) density was also lower in detubulated myocytes over the range of voltages (-50 to +100 mV) and internal [Na] ([Na](i)) investigated (7-22 mM). At [Na](i) = 10 mM and -20 mV, I(pump) density was reduced by 39% in detubulated myocytes (0.28 +/- 0.02 vs. 0.17 +/- 0.03 pA/pF), but the apparent K(m) for [Na](i) was unchanged (16.9 +/- 0.4 vs. 17.0 +/- 0.3 mM). These results indicate that although thet-tubules represent only approximately 32% of the total sarcolemma, they contribute approximately 60% to the total I(NCX) and I(pump). Thus, the functional density of NCX and Na/K pump in the t-tubules is 3-3.5-fold higher than in the external sarcolemma.

Animals↗
PubMed2003

Factors affecting capacitive current diversion with a uterine resectoscope: an in vitro study.

STUDY OBJECTIVE: To evaluate electrosurgical waveform, generator type, and electrode integrity as variables in capacitive induction of current on the external sheath of a resectoscope in open-circuit conditions. DESIGN: In vitro, laboratory, comparative study (Canadian Task Force classification CII-1). SETTING: Surgical laboratory. INSTRUMENTATION: Three ValleyLab radiofrequency (RF) electrosurgical generators (ESU), Force-2, Force-4, and Force-F/X; a resectoscope (Storz 50 series); and rollerball electrodes, both intact and with two types of standard insulation defects (lateral and circumferential) placed in two locations: distally, beyond the end of the telescope, and proximally, beside the distal aspect of the telescope. A Dynatek ESU analyzer was used to record current and wattage on electrodes and the external sheath. MEASUREMENTS AND MAIN RESULTS: With intact insulation, current was not disproportionately induced on the external sheath of the resectoscope regardless of ESU, power, or waveform. Proximally located electrode insulation defects allowed induction of most of the generator's output to the external sheath when high-voltage modulated outputs were used, and the risk varied somewhat with the ESU. There was no such induction at any power setting or with any insulation defect when low-voltage (cutting) outputs were tested. CONCLUSION: In the presence of proximal electrode defects, high-voltage currents may contribute to thermal injury to the lower genital tract during RF resectoscopic surgery.

Electric Capacitance↗
PubMed2003

Dynamin regulates focal exocytosis in phagocytosing macrophages.

Phagocytosis in macrophages is thought to involve insertion of cytoplasmic vesicles at sites of membrane expansion before particle ingestion ("focal" exocytosis). Capacitance (Cm) measurements of cell surface area were biphasic, with an initial rise indicative of exocytosis followed by a fall upon phagocytosis. Unlike other types of regulated exocytosis, the Cm rise was insensitive to intracellular Ca2+, but was inhibited by guanosine 5'-O-(2-thio)diphosphate. Particle uptake, but not Cm rise, was affected by phosphatidylinositol 3-kinase inhibitors. Inhibition of actin polymerization eliminated the Cm rise, suggesting possible coordination between actin polymerization and focal exocytosis. Introduction of anti-pan-dynamin IgG blocked Cm changes, suggesting that dynamin controls focal exocytosis and thereby phagocytosis. Similarly, recombinant glutathione S-transferase*amphiphysin-SH3 domain, but not a mutated form that cannot bind to dynamin, inhibited both focal exocytosis and phagocytosis. Immunochemical analysis of endogenous dynamin distribution in macrophages revealed a substantial particulate pool, some of which localized to a presumptive endosomal compartment. Expression of enhanced green fluorescent protein*dynamin-2 showed a motile dynamin pool, a fraction of which migrated toward and within the phagosomal cup. These results suggest that dynamin is involved in the production and/or movement of vesicles from an intracellular organelle to the cell surface to support membrane expansion around the engulfed particle.

Actins↗
PubMed2004

Forward-viewing CMUT arrays for medical imaging.

This paper reports the design and testing of forward-viewing annular arrays fabricated using capacitive micromachined ultrasonic transducer (CMUT) technology. Recent research studies have shown that CMUTs have broad frequency bandwidth and high-transduction efficiency. One- and two-dimensional CMUT arrays of various sizes already have been fabricated, and their viability for medical imaging applications has been demonstrated. We fabricated 64-element, forward-viewing annular arrays using the standard CMUT fabrication process and carried out experiments to measure the operating frequency, bandwidth, and transmit/receive efficiency of the array elements. The annular array elements, designed for imaging applications in the 20 MHz range, had a resonance frequency of 13.5 MHz in air. The immersion pulse-echo data collected from a plane reflector showed that the devices operate in the 5-26 MHz range with a fractional bandwidth of 135%. The output pressure at the surface of the transducer was measured to be 24 kPa/V. These values translate into a dynamic range of 131.5 dB for 1-V excitation in 1-Hz bandwidth with a commercial low noise receiving circuitry. The designed, forward-viewing annular CMUT array is suitable for mounting on the front surface of a cylindrical catheter probe and can provide Doppler information for measurement of blood flow and guiding information for navigation through blood vessels in intravascular ultrasound imaging.

Electric Capacitance↗
PubMed2005

The C-terminus of prestin influences nonlinear capacitance and plasma membrane targeting.

Prestin is a unique molecular-motor protein expressed in the lateral plasma membrane of outer hair cells (OHC) in the organ of Corti of the mammalian cochlea. It is thought that prestin undergoes conformational changes driven by the cell's membrane potential. The resulting alterations in OHC-length are assumed to constitute the cochlear amplifier. Prestin is a member of the anion solute carrier family 26 (SCL26A), but it is different from other family members in its unique function of voltage-driven motility. Because the C-terminus is the least conserved region in the family, we investigated its influence with a series of deletion, point and chimeric mutants. The function and cellular expression of mutants were examined in a heterologous expression system by measurement of nonlinear capacitance (NLC) and immunofluorescence. Each mutant produced a unique mixture of patterns of cell morphologies, which were classified as to the location of prestin within the cell. The data from deletion mutants (Del516, Del525, Del630, Del590, Del709, Del719) revealed that nearly the full length (>708 amino acids) of the protein was required for normal prestin expression and function. Since most deletion mutations eliminated plasma membrane targeting, chimeric proteins were constructed by fusing prestin, at amino acid 515 or 644, with the homologous portion of the C-terminus from the two most closely related SLC26A members, pendrin and putative anion exchanger 1. These chimeric proteins were again improperly (but differently) targeted than simple truncation mutants, and all lacked functional phenotype. When two of the potential basolateral membrane-targeting motifs were mutated (Y520A/Y526A), incomplete plasma membrane expression was seen. We also show that some double point mutations (V499G/Y501H) fully express in the plasma membrane but lack NLC. These non-charged amino acids may have unrevealed important roles in prestin's function. Together, these data suggest that certain specific sequences and individual amino acids in the C-terminus are necessary for correct cellular distribution and function.

Animals↗
PubMed2005

Effect of input resistance voltage-dependency on DC estimate of membrane capacitance in cardiac myocytes.

The measure of membrane capacitance (C(m)) in cardiac myocytes is of primary importance as an index of their size in physiological and pathological conditions, and for the understanding of their excitability. Although a plethora of very accurate methods has been developed to access C(m) value in single cells, cardiac electrophysiologists still use, in the majority of laboratories, classical direct current techniques as they have been established in the early days of cardiac cellular electrophysiology. These techniques are based on the assumption that cardiac membrane resistance (R(m)) is constant, or changes negligibly, in a narrow potential range around resting potential. Using patch-clamp whole-cell recordings, both in current-clamp and voltage-clamp conditions, and numerical simulations, we document here the voltage-dependency of R(m), up to -45% of its resting value for 10-mV hyperpolarization, in resting rat ventricular myocytes. We show how this dependency makes classical protocols to misestimate C(m) in a voltage-dependent manner (up to 20% errors), which can dramatically affect C(m)-based calculations on cell size and on intracellular ion dynamics. We develop a simple mechanistic model to fit experimental data and obtain voltage-independent estimates of C(m), and we show that accurate estimates can also be extrapolated from the classical approach.

Animals↗
PubMed2005

Influence of external pH on two types of low-voltage-activated calcium currents in primary sensory neurons of rats.

The influence of extracellular pH (pH(o)) on low-voltage-activated calcium channels of acutely isolated DRG neurons of rats was examined using the whole cell patch-clamp technique. It has been found that in the neurons of middle size with capacitance C=60+/-4.8 pF (mean+/-S.E., n=8) extracellular acidification from pH(o) 7.35 to pH(o) 6.0 significantly and reversibly decreased LVA calcium current densities by 75+/-3.7%, shifted potential for half-maximal activation to more positive voltages by 18.7+/-0.6 mV with significant reduction of its voltage dependence. The half-maximal potential of steady-state inactivation shifted to more positive voltages by 12.1+/-1.7 mV (n=8) and also became less voltage dependent. Dose-response curves for the dependence of maximum values of LVA currents on external pH in neurons of middle size have midpoint pK(a)=6.6+/-0.02 and hill coefficient h=0.94+/-0.04 (n=5). In small cells with capacitance C=26+/-3.6 pF (n=5), acidosis decreased LVA calcium current densities only by 15.3+/-1.3% and shifted potential for half-maximal activation by 5.5+/-1.0 mV with reduction of its voltage dependence. Half-maximal potential of steady-state inactivation shifted to more positive voltages by 10+/-1.6 mV (n=4) and also became less voltage dependent. Dose-response curves for the dependence of maximum values of LVA currents on external pH in neurons of small size have midpoint pK(a)=7.9+/-0.04 and hill coefficient h=0.25+/-0.1 (n=4). These two identified types of LVA currents besides different pH sensitivity demonstrated different kinetic properties. The deactivation of LVA currents with weak pH sensitivity after switching off depolarization to -30 mV had substantially longer decay time than do currents with strong pH sensitivity (tau(d) approximately 5 ms vs. 2 ms respectively). It was found that the prolongation of depolarization steps slows the subsequent deactivation of T-type currents in small DRG neurons. Deactivation traces in these neurons were better described by the sum of two exponentials. Thus, we suppose that T-type channels in small DRG neurons are presented mostly by alpha1I subunit. We suggest that these two types of LVA calcium channels with different sensitivity to external pH can be differently involved in the origin of neuropathic changes.

Animals↗