Biomedical subjects

T Oshima

Publications and source records attributed to T Oshima.

At least 55 records · Page 3Linked to original sources

PubMed2001

High thermal stability of 3-isopropylmalate dehydrogenase from Thermus thermophilus resulting from low DeltaC(p) of unfolding.

To characterize the thermal stability of 3-isopropylmalate dehydrogenase (IPMDH) from an extreme thermophile, Thermus thermophilus, urea-induced unfolding of the enzyme and of its mesophilic counterpart from Escherichia coli was investigated at various temperatures. The unfolding curves were analyzed with a three-state model for E.coli IPMDH and with a two-state model for T.thermophilus IPMDH, to obtain the free energy change DeltaG degrees of each unfolding process. Other thermodynamic parameters, enthalpy change DeltaH, entropy change DeltaS and heat capacity change DeltaC(p), were derived from the temperature dependence of DeltaG degrees. The main feature of the thermophilic enzyme was its lower dependence of DeltaG degrees on temperature resulting from a low DeltaC(p). The thermophilic IPMDH had a significantly lower DeltaC(p), 1.73 kcal/mol.K, than that of E.coli IPMDH (20.7 kcal/mol.K). The low DeltaC(p) of T.thermophilus IPMDH could not be predicted from its change in solvent-accessible surface area DeltaASA. The results suggested that there is a large structural difference between the unfolded state of T.thermophilus and that of E.coli IPMDH. Another responsible factor for the higher thermal stability of T.thermophilus IPMDH was the increase in the most stable temperature T(s). The DeltaG degrees maximum of T.thermophilus IPMDH was much smaller than that of E.coli IPMDH. The present results clearly demonstrated that a higher melting temperature T(m) is not necessarily accompanied by a higher DeltaG degrees maximum.

3-Isopropylmalate Dehydrogenase↗

PubMed2001

Crystal structures of mutants of Thermus thermophilus IPMDH adapted to low temperatures.

Random mutagenesis on thermophilic 3-isopropylmalate dehydrogenases (IPMDH; EC 1.1.1.85) produced mutant enzymes which adapt to low temperatures. These mutants had higher activity at lower temperatures than the wild-type enzyme without losing high thermostability. Here we report three structures of the mutants of Thermus thermophilus IPMDH determined by X-ray diffraction which was adapted to a low-temperature environment. Two of them have unstable coenzyme binding states and the other one probably has a stable substrate binding state. The present research suggests that the adaptation is correlated with the binding of either coenzyme or the substrate.

3-Isopropylmalate Dehydrogenase↗

PubMed2001

Adaptation of a thermophilic enzyme, 3-isopropylmalate dehydrogenase, to low temperatures.

Random mutagenesis coupled with screening of the active enzyme at a low temperature was applied to isolate cold-adapted mutants of a thermophilic enzyme. Four mutant enzymes with enhanced specific activities (up to 4.1-fold at 40 degrees C) at a moderate temperature were isolated from randomly mutated Thermus thermophilus 3-isopropylmalate dehydrogenase. Kinetic analysis revealed two types of cold-adapted mutants, i.e. k(cat)-improved and K(m)-improved types. The k(cat)-improved mutants showed less temperature-dependent catalytic properties, resulting in improvement of k(cat) (up to 7.5-fold at 40 degrees C) at lower temperatures with increased K(m) values mainly for NAD. The K(m)-improved enzyme showed higher affinities toward the substrate and the coenzyme without significant change in k(cat) at the temperatures investigated (30-70 degrees C). In k(cat)-improved mutants, replacement of a residue was found near the binding pocket for the adenine portion of NAD. Two of the mutants retained thermal stability indistinguishable from the wild-type enzyme. Extreme thermal stability of the thermophilic enzyme is not necessarily decreased to improve the catalytic function at lower temperatures. The present strategy provides a powerful tool for obtaining active mutant enzymes at lower temperatures. The results also indicate that it is possible to obtain cold-adapted mutant enzymes with high thermal stability.

3-Isopropylmalate Dehydrogenase↗

PubMed2001

Analysis of the effect of accumulation of amino acid replacements on activity of 3-isopropylmalate dehydrogenase from Thermus thermophilus.

A newly selected cold-adapted mutant 3-isopropylmalate dehydrogenase (IPMDH) from a random mutant library was a double mutant containing the mutations I11V and S92F that were found in cold-adapted mutant IPMDHs previously isolated. To elucidate the effect of each mutation on enzymatic activity, I11V and six multiple mutant IPMDHs were constructed and analyzed. All of the multiple mutant IPMDHs were found to be improved in catalytic activity at moderate temperatures by increasing the k(cat) with a simultaneous increase of K(m) for the coenzyme NAD(+). k(cat) was improved by a decrease in the activation enthalpy, DeltaH( not equal). The multiple mutants did not show large reduction in thermal stability, and one of them showed enhanced thermal stability. Mutation from I11 to V was revealed to have a stabilizing effect. Mutants showed increased thermal stability when the mutation I11V was combined. This indicates that it is possible to construct mutants with enhanced thermal stability by combining stabilizing mutation. No additivity was observed for the thermodynamic properties of catalytic reaction in the multiple mutant IPMDHs, implying that the structural changes induced by the mutations were interacting with each other. This indicates that careful and detailed tuning is required for enhancing activity in contrast to thermal stability.

3-Isopropylmalate Dehydrogenase↗

PubMed2001

The anxiolytic effects of the 5-hydroxytryptamine-1A agonist tandospirone before otolaryngologic surgery.

UNLABELLED: We studied 160 ASA I or II patients undergoing elective otolaryngologic surgery in order to compare the anxiolytic effects of a novel 5-hydroxytryptamine-1A agonist, tandospirone, with diazepam. To monitor preoperative anxiety, the following variables were used: systolic and diastolic arterial pressure, heart rate, and the state anxiety score yielded by the Spielberger State-Trait Anxiety Inventory. We performed pretreatment evaluation on the day before surgery and posttreatment examination immediately after entry into the operating room. In a double-blinded, randomized design, four groups of 40 patients each received one of the following oral medications 90 min before entry into the operating room: 1) tandospirone 10 mg (T10 group); 2) tandospirone 30 mg (T30 group); 3) diazepam 10 mg (D group); or 4) placebo (P group). After premedication, the State-Trait Anxiety Inventory state anxiety decreased in the T10 (P < 0.02), T30 (P < 0.02), and D groups (P < 0.001), but it increased in the P group (P < 0.001). Tandospirone, 10 and 30 mg, safely reduced preoperative anxiety to a similar extent as oral diazepam 10 mg in patients undergoing elective otolaryngologic surgery. IMPLICATIONS: Oral tandospirone reduces preoperative anxiety to a similar extent as oral diazepam in patients undergoing elective otolaryngologic surgery. This finding implies that tandospirone can be used as an oral premedicant drug for relieving anxiety before surgery.

Adolescent↗

PubMed2001

Calorie restriction reduced blood pressure in obesity hypertensives by improvement of autonomic nerve activity and insulin sensitivity.

Association between obesity and hypertension has been well recognized. A reduction in the body weight of over-weight hypertensive patients is a recommended lifestyle modification. The purpose of our study is to examine the relationship of insulin sensitivity and autonomic nervous activity with reduction of blood pressure by the calorie restriction. We evaluated the heart rate variability, nocturnal change of blood pressure and insulin resistance before and after a short-term low-calorie diet in 12 overweight essential hypertensives. After a week of standard diet (2000 kcal), 2 weeks of low-calorie diet (800 kcal) with normal sodium content induced a significant reduction in body mass index, triglyceride, fasting immunoreactive protein, homeostasis model assessment as an index of insulin resistance, and urinary excretion of sodium and potassium. Systolic blood pressure was significantly reduced both in daytime and night-time after the low-calorie diet (daytime, 134.5+/-6.0 to 122.0+/-4.1 mmHg; night-time, 126.8+/-5.2 to 113.4+/-7.2 mmHg). In daytime, diastolic blood pressure was also reduced (90.3+/-2.1 to 88.1+/-4.8 mmHg). Although heart rate was not significantly reduced, a rise of high frequency in night-time (346+/-82 to 572+/-108 ms2) and a fall of low frequency/high frequency in day-time (3.5+/-0.4 to 2.6+/-0.1) was significant after a low-calorie diet. In conclusion, weight loss by low-calorie diet with a constant intake of sodium, reduced blood pressure in obese hypertensives by improvement of vagal nervous activity and insulin resistance.

Adult↗

PubMed2001

The expression of apoptosis-related proteins in the aged cochlea of Mongolian gerbils.

OBJECTIVE: Apoptotic changes have been reported in the aged gerbil cochlea and are speculated to be one of the principal causes of presbyacusis. The objective of the study was to determine the underlying mechanism of apoptotic change in the aged gerbil cochlea. STUDY DESIGN: Prospective controlled animal study. METHODS: We examined the tissue distribution of bcl-2, bax, caspase-3p20, and caspase-3p32 using immunohistochemical techniques in the young and aged gerbil cochlea, together with the measurement of the distortion product of otoacoustic emission (DPOAE). RESULTS: Aged gerbils showed a significant reduction of the DPOAE amplitude as compared with that of the young gerbils, suggesting a disturbance of the auditory function in the aged cochlea. There was a significant decrease in the number of bcl-2-positive cells in the aged gerbils. The expression of bax in the aged group was slightly increased but did not significantly differ from that in the young gerbils. A significantly increased number of caspase-3p20-positive cells was observed in the organ of Corti, spiral ganglion, and lateral wall of cochlea in the aged gerbils as compared with those of the young gerbils. There was no significant difference in the expression levels of caspase-3p32 between the young and aged groups. In the aged cochlea, the degree of deterioration of DPOAE responses was compatible with those of both the reduction of bcl-2 and the activation of caspase-3p20. CONCLUSION: These data suggest that the suppression of bcl-2 protein expression may lead to apoptosis-induced presbyacusis through activation of caspase-3 in the aged gerbil cochlea.

Age Factors↗

PubMed2001

GJB2 (connexin 26) mutations and childhood deafness in Thailand.

HYPOTHESIS: The purpose of this study was to elucidate whether GJB2 mutations are responsible for childhood deafness in Southeast Asia. BACKGROUND: GJB2 mutations are responsible for a large part of childhood deafness in many countries. In Whites, there is a common mutation (35delG) that accounts for about 70 to 80% of the GJB2 mutations. Previously, we and others reported a common GJB2 mutation (235delC) in Japanese patients with prelingual deafness. The association of the 235delC mutation with a single haplotype suggested a founder effect of the mutation. METHODS: We analyzed the GJB2 gene in 17 deaf patients from 12 unrelated families in Thailand. Genomic DNA was extracted from peripheral lymphocytes of each patient and the entire coding region of the GJB2 gene was sequenced. RESULTS: GJB2 mutations were found in 4 patients in 3 families. Patient 1 was a homozygote of 235delC. Patient 2 was a compound heterozygote of 235delC and W24X (71G --> A). Patient 3A and 3B (in 1 family) were heterozygotes of a novel mutation M34L (100A --> T). CONCLUSION: The 235delC mutation may be widely distributed in Asian countries outside of Japan.

Child↗

PubMed2001

Design, X-ray crystallography, molecular modelling and thermal stability studies of mutant enzymes at site 172 of 3-isopropylmalate dehydrogenase from Thermus thermophilus.

The relationship between the structure and the thermostability of the 3-isopropylmalate dehydrogenase from Thermus thermophilus was studied by site-directed mutation of a single Ala residue located at the domain interface. The crystal structures of three mutant enzymes, replacing Ala172 with Gly, Val and Phe, were successfully determined at 2.3, 2.2 and 2.5 A resolution, respectively. Substitution of Ala172 by relatively 'short' residues (Gly, Val or Ile) enlarges or narrows the cavity in the vicinity of the C(beta) atom of Ala172 and the thermostablity of the enzyme shows a good correlation with the hydrophobicity of the substituted residues. Substitution of Ala172 by the 'longer' residues Leu or Phe causes a rearrangement of the domain structure, which leads to a higher thermostability of the enzymes than that expected from the hydrophobicity of the substituted residues. Mutation of Ala172 to negatively charged residues gave an unexpected result: the melting temperature of the Asp mutant enzyme was reduced by 2.7 K while that of the Glu mutant increased by 1.8 K. Molecular-modelling studies indicated that the glutamate side chain was sufficiently long that it did not act as a buried charge as did the aspartate, but instead protruded to the outside of the hydrophobic cavity and contributed to the stability of the enzyme by enhancing the packing of the local side chains and forming an extra salt bridge with the side chain of Lys175.

3-Isopropylmalate Dehydrogenase↗

PubMed2001

Quinone profiles of Thermoplasma acidophilum HO-62.

Quinones of Thermoplasma acidophilum HO-62 were analyzed by high-performance liquid chromatography, mass spectrometry, and nuclear magnetic resonance. Menaquinone, methionaquinone, and 2-trans and 2-cis forms of thermoplasmaquinone were identified. The relative amount of thermoplasmaquinone increased under anaerobic conditions, and those of menaquinone and methionaquinone increased under aerobic conditions.

Chromatography, High Pressure Liquid↗

PubMed2001

Regulation and distribution of MAdCAM-1 in endothelial cells in vitro.

Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is a 60-kDa endothelial cell adhesion glycoprotein that regulates lymphocyte trafficking to Peyer's patches and lymph nodes. Although it is widely agreed that MAdCAM-1 induction is involved in chronic gut inflammation, few studies have investigated regulation of MAdCAM-1 expression. We used two endothelial lines [bEND.3 (brain) and SVEC (high endothelium)] to study the signal paths that regulate MAdCAM-1 expression in response to tumor necrosis factor (TNF)-alpha using RT-PCR, blotting, adhesion, and immunofluorescence. TNF-alpha induced both MAdCAM-1 mRNA and protein in a dose- and time-dependent manner. This induction was tyrosine kinase (TK), p42/44, p38 mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-kappa B/poly-ADP ribose polymerase (PARP) dependent. Because MAdCAM-1 is regulated via MAPKs, we examined mitogen/extracellular signal-regulated kinase (MEK)-1/2 activation in SVEC. We found that MEK-1/2 is activated by TNF-alpha within minutes and is dependent on TK and p42/44 MAPKs. Similarly, TNF-alpha activated NF-kappa B through TK, p42/44, p38 MAPKs, and PARP pathways in SVEC cells. MAdCAM-1 was also shown to be frequently distributed to endothelial junctions both in vitro and in vivo. Cytokines like TNF-alpha stimulate MAdCAM-1 in high endothelium via TK, p38, p42/22 MAPKs, and NF-kappa B/PARP. MAdCAM-1 expression requires NF-kappa B translocation through both direct p42/44 and indirect p38 MAPK pathways in high endothelial cells.

Alkaloids↗

PubMed2001

Effect of estrogen replacement therapy on endothelial function in peripheral resistance arteries in normotensive and hypertensive postmenopausal women.

Both menopause and hypertension are associated with endothelial dysfunction and are risk factors for coronary heart disease. We evaluated forearm resistance artery endothelial function in hypertensive postmenopausal women (HPW, n=57) and compared it with endothelial function in normotensive postmenopausal women (NPW, n=67). In addition, we evaluated the effects of long-term estrogen replacement therapy (ERT, conjugated equine estrogen at a dose of 0.625 mg daily for 12 weeks) on endothelial function in HPW (n=10) and NPW (n=35). Forearm blood flow (FBF) was measured by strain-gauge plethysmography during reactive hyperemia to assess endothelium-dependent vasodilation and after sublingual nitroglycerin (NTG) administration to assess endothelium-independent vasodilation. Basal FBF was similar in the NPW and HPW groups. The FBF in the HPW group during reactive hyperemia was significantly lower than that in the NPW group. Increases in FBF after NTG were similar in the 2 groups. ERT decreased the LDL cholesterol concentration and circulating ACE activity and increased estradiol and HDL cholesterol in both groups. Basal blood pressures, heart rate, FBF, and body weight did not change with ERT. After 12 weeks of ERT, the maximal FBF response during reactive hyperemia increased significantly in both groups. The improvement in reactive hyperemia after ERT was significantly greater in the HPW group than in the NPW group (49+/-8 versus 17+/-5%, P<0.05). Changes in FBF after sublingual NTG administration were similar before and after 12 weeks of ERT. These findings suggest that continued ERT improves forearm resistance artery endothelial function in postmenopausal women and that this beneficial effect is greater in patients that are hypertensive.

Blood Pressure↗

PubMed2001

Apoptosis is not increased in myocardium overexpressing type 2 angiotensin II receptor in transgenic mice.

To determine whether angiotensin type 2 (AT(2)) receptor stimulation induces apoptosis in cardiomyocytes in vivo, we developed transgenic mice overexpressing the AT(2) receptor in a cardiac-specific manner, using the alpha-myosin heavy-chain promoter. Ten- to 12-week-old male homozygous transgenic mice (n=44) and wild-type mice (n=44) were used. Both transgenic and wild-type mice were given either saline (control), a subpressor dose of angiotensin II (100 ng. kg(-1). min(-1)), a pressor dose of angiotensin II (1000 ng. kg(-1). min(-1)) for 14 days, a pressor dose of angiotensin II for 28 days to investigate the effects of stimulation on both angiotensin type 1 (AT(1)) and AT(2) receptors, the AT(1) antagonist L158809 alone, or a combination of angiotensin II (1000 ng. kg(-1). min(-1)) and L158809 for 14 days to investigate the effects of selective AT(2) receptor stimulation. Apoptosis was analyzed in paraffin-embedded ventricular sections by the terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL) technique. In both transgenic and wild-type mice, administration of a subpressor dose of angiotensin II, L158809, or a combination of angiotensin II and L158809 did not significantly affect the tail-cuff blood pressure or heart-to-body weight ratio, whereas administration of a pressor dose of angiotensin II for 14 or 28 days significantly increased blood pressure and the heart-to-body weight ratio. However, there was no statistical difference between the effects of angiotensin II in transgenic and wild-type mice. The number of TUNEL-positive nuclei was approximately 0 to 10 per 100 000 cardiomyocytes, with no difference between transgenic and wild-type mice, regardless of saline infusion or any stimulation. In infarcted canine myocardial tissue sections for positive control, the number of TUNEL-positive nuclei was increased by 13.8 to 19.1 times compared with those in the noninfarcted myocardium. In conclusion, angiotensin II infusion for a period of 28 days failed to induce cardiomyocyte apoptosis regardless of the presence or absence of cardiac AT(2) receptor overexpression. It is unlikely that in mice the AT(2) receptor is a strong signal to induce cardiomyocyte apoptosis in vivo.

Angiotensin II↗

PubMed2001

Effects of angiotensin-(1-7) on forearm circulation in normotensive subjects and patients with essential hypertension.

Previous animal studies have shown that angiotensin (Ang)-(1-7) is a biologically active component of the renin-angiotensin system, acting as a vasoactive agent, and may play a role in the blood pressure regulation. There is little information, however, on the effect of Ang-(1-7) on human circulation or the mechanism of its action. To investigate the effect of Ang-(1-7) on forearm circulation and to determine whether this effect is altered in patients with essential hypertension, we measured change in forearm blood flow using venous occlusion plethysmography in response to intra-arterial infusion of Ang-(1-7) (10(-10), 10(-9), and 10(-8) mol/min; for 5 minutes) in normotensive control subjects (n=8) and patients with essential hypertension (n=8). Infusion of Ang-(1-7) significantly increased the forearm blood flow response in a dose-dependent manner in both normotensive control subjects (28.7+/-9.7%, at 10(-8) mol/min; P<0.05) and hypertensive patients (31.8+/-15.2%, at 10(-8) mol/min; P<0.05). The vasodilatory effect of Ang-(1-7) was similar in the two groups. Intra-arterial infusion of N(G)-monomethyl-L-arginine, a nitric oxide synthesis inhibitor, did not alter the forearm blood flow response to Ang-(1-7) in either group. These findings suggest that Ang-(1-7) causes vasodilation in forearm circulation of normotensive subjects and patients with essential hypertension through a pathway that is independent of nitric oxide synthesis.

Analysis of Variance↗

PubMed2001

Quantitative assessment of the pharyngeal airway by dynamic magnetic resonance imaging in obstructive sleep apnea syndrome.

Dynamic changes in the pharyngeal airway of patients with obstructive sleep apnea syndrome (OSAS) were evaluated by quantitating the findings of real-time imaging performed during wakefulness and spontaneous sleep by means of dynamic magnetic resonance imaging (MRI). Six patients with OSAS and 3 non-OSAS subjects, selected prospectively and randomly, underwent polysomnography and dynamic MRI. The cross-sectional areas of the soft palate and oropharynx and the anterior-posterior airway dimensions seen during wakefulness and spontaneous sleep were calculated by US National Institutes of Health imaging software. On the basis of a case control study, comparisons were made with age-matched and body mass index-matched obese non-OSAS snorers. Spontaneous sleep caused significant obstruction and narrowing of various sites of the pharyngeal airway in the OSAS patients, but not in the non-OSAS subjects. During wakefulness, the non-OSAS subjects showed no marked narrowing of the pharyngeal airways, whereas a transient but significant narrowing was observed in the OSAS patients. The mean values of both the cross-sectional area and the anterior-posterior diameter at the soft palate were significantly reduced by spontaneous sleep in the OSAS patients. Dynamic MRI in awake OSAS patients shows promise as a routine diagnostic tool for localizing the upper airway collapse for appropriate selection of surgical therapy.

Adult↗

PubMed2001

Sodium chloride loading does not alter endothelium-dependent vasodilation of forearm vasculature in either salt-sensitive or salt-resistant patients with essential hypertension.

The purpose of this study was to determine whether a high NaCl intake impairs endothelium-dependent and -independent vasodilation of forearm circulation in salt sensitive (SS) patients with essential hypertension. We evaluated the effects of intra-arterial acetylcholine (ACh) and isosorbide dinitrate (ISDN) on forearm hemodynamics in 29 patients with essential hypertension, while consuming a low NaCl (50 mmol/d) or high Na Cl (340 mmol/d) diet for 1 week. The forearm blood flow (FBF) was measured by strain-gauge plethysmography. Patients were classified as SS (n=12) or salt resistant (SR; n=17) based on salt-induced changes in blood pressures. The FBF responses of ACh and ISDN were similar in the SS and SR patients while on either NaCl diet, and was not altered by salt loading (ACh, SS: low NaCl 22.8+/-4.3 vs. high NaCl 21.1+/-3.6 ml/min per 100 ml, SR: low NaCl 22.5+/-4.0 vs. high NaCl 23.3+/-4.1 ml/min per 100 ml; ISDN, SS: low NaCl 13.9+/-2.1 vs. high NaCl 14.1+/-2.2 ml/min per 100 ml, SR: low NaCl 13.8+/-2.3 vs. high NaCl 14.0+/-2.2 ml/min per 100 ml). There were no significant differences in the vascular responses to ACh and ISDN in the presence of N(G)-monomethyl-L-arginine, a nitric oxide synthase inhibitor, in either group for either NaCl diet. These findings suggest that forearm resistance artery endothelial function may not be influenced by salt loading in either SS patients which finding may play a role in determining salt sensitivity in patients with essential hypertension or SR patients.

Diet, Sodium-Restricted↗

PubMed2001

The role of p38 MAP kinase in hydrogen peroxide mediated endothelial solute permeability.

OBJECTIVE: The purpose of this study was to determine the contribution of p38 MAP kinase activity during hydrogen peroxide mediated increased endothelial solute permeability. We also sought to identify the role of p38 MAP kinase-mediated changes in endothelial cell architecture due to hydrogen peroxide challenge. METHODS: Hydrogen peroxide mediated permeability of HUVEC was determined with and without inhibition of p38 MAP kinase by SB202190. Hydrogen peroxide mediated rearrangement of the endothelial actin cytoskeleton and junctional proteins occludin and ZO-1 were observed by immunofluorescence microscopy. RESULTS: Hydrogen peroxide treatment of endothelial monolayers caused a significant increase in solute permeability over a ninety-minute time period. Oxidant-mediated permeability and phosphorylation of p38 MAP kinase was significantly attenuated by SB 202190. Immunofluorescent staining for the tight junctional proteins occludin and ZO-1 demonstrated that oxidant challenge caused a loss of endothelial tight junction organization. Rhodamine phalloidin staining of the actin cytoskeleton showed that hydrogen peroxide stimulated increased stress fiber formation with concomitant gap formation between adjacent endothelial cells. Inhibition of p38 MAP kinase during oxidant challenge significantly attenuated actin stress fiber formation and prevented gap formation. CONCLUSIONS: These data demonstrate that p38 MAP kinase activity is involved in hydrogen peroxide mediated permeability, stress fiber formation, and intracellular gap formation.

Actin Cytoskeleton↗

PubMed2001

Mechanical vibratory stimulation of feline forepaw skin induces long-lasting potentiation in the secondary somatosensory cortex.

We investigated the long-lasting effects of mechanical vibratory stimulation of the skin on the excitability of feline cortical neurons in the forelimb areas of the primary (SI) and secondary (SII) somatosensory cortices. Conditioning mechanical stimuli were 300 bursts of 10 pulses at 200 Hz delivered with a 10-s interburst interval from a mechanical stimulator. Test field potentials and unit discharges were evoked by electrical stimulation to the ventral posterolateral thalamic nucleus (VPL) or by single mechanical stimuli applied to the skin. In SII, the mechanical burst stimulation to the skin increased the amplitudes of field potentials and the frequency of unit discharges elicited by single mechanical stimuli applied to the skin. The vibratory conditioning stimulus also produced a similar potentiation of the VPL-evoked field potentials (126-139% increase in amplitude, P < 0.05) with an associated increase in firing rates of extracellularly recorded neuronal activity (117%, P < 0.001). These potentiations persisted through the entire experimental period of 120 min. The translaminar current source density analysis calculated from the VPL-evoked field potentials increased to 127% of the control value (P < 0.01). In contrast, in SI we observed no significant changes in the field potential amplitudes or in the currents generated in superficial layers (91-117%). Taken together with the previous finding that tetanic electrical stimulation of VPL induces long-lasting potentiation of the VPL-evoked cortical responses in SII but not of those in SI, the present results suggest that SII has a large capacity for the rapid functional plasticity involved in the learning that occurs during repeated tactile experiences.

Animals↗