bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodal output mapping of human central motor representation on different spatial scales
Authors: Classen Joseph , Knorr Uwe , Werhahn Konrad J. , Schlaug Gottfried , Kunesch Erwin , Cohen Leonardo G. , Seitz Rüdiger J. , Benecke Reiner 
Published: September 2004

Non‐invasive mapping by focal transcranial magnetic stimulation (TMS) is frequently used to investigate cortical motor function in the intact and injured human brain. We examined how TMS‐derived maps relate to the underlying cortical anatomy and to cortical maps generated by functional imaging studies.
The centres of gravity (COGs) of TMS maps of the first dorsal intersosseus muscle (FDI) were integrated into 3‐D magnetic resonance imaging (MRI) data sets in eleven subjects. In seven of these subjects the TMS‐derived COGs were compared with the COG of regional cerebral blood flow increases using positron emission tomography (PET) in an index finger flexion protocol.
Mean TMS‐derived COG projections were located on the posterior lip of the precentral gyrus and TMS‐derived COG projections were in close proximity to the mean PET‐derived COG, suggesting that the two methods reflect activity of similar cortical elements.
Criteria for a reliable assessment of the COG and the number of positions with a minimum amplitude of two‐thirds of the maximum motor‐evoked potential (T3Ps) were determined as a function of the number of stimuli and extension of the stimulation field. COGs and T3Ps were compared with an estimate of the size of the human motor cortex targeting α‐motoneurons of forearm muscles. This comparison suggests that TMS can retrieve spatial information on cortical organization below the macroanatomic scale of cortical regions.
Finally, we studied the cortical representation of hand muscles in relation to facial and foot muscle representations and investigated hemispherical asymmetries. We did not find any evidence for a different ipsi‐ or contralateral representation of the mentalis muscle. Also, no difference was found between FDI representations on the dominant versus the non‐dominant hemisphere.
Role of domain I of neuronal Ca2+ channel α1 subunits in G protein modulation
Authors: Stephens Gary J. , Cantí Carles , Page Karen M. , Dolphin Annette C. 
Published: September 2004

We studied the G protein inhibition of heteromultimeric neuronal Ca2+ channels by constructing a series of chimeric channels between the strongly modulated α1B subunit and the α1E(rbEII) subunit, which showed no modulation.
In parallel studies, α1 subunit constructs were co‐expressed together with the accessory Ca2+ channel α2‐δ and β2a subunits in mammalian (COS‐7) cells and Xenopus oocytes. G protein inhibition of expressed Ca2+ channel currents was induced by co‐transfection of Gβ1 and Gγ2 subunits in COS‐7 cells or activation of co‐expressed dopamine (D2) receptors by quinpirole (100 nm) in oocytes.
The data indicate that transfer of the α1B region containing the N‐terminal, domain I and the I‐II loop (i.e. the α1B1‐483 sequence), conferred G protein modulation on α1E(rbEII), both in terms of a slowing of activation kinetics and a reduction in current amplitude.
In contrast, the data are not consistent with the I‐II loop and/or the C‐terminal forming a unique site for G protein modulation.
Caesium blocks depolarizing after‐potentials and phasic firing in rat supraoptic neurones
Authors: Ghamari‐Langroudi Masoud , Bourque Charles W. 
Published: September 2004

The effects of Cs+ on the action potential, post‐train after‐hyperpolarization (AHP), Ca2+‐dependent post‐spike depolarizing after‐potential (DAP) and phasic firing were examined during intracellular recordings from magnocellular neurosecretory cells (MNCs) in superfused rat hypothalamic explants.
Extracellular Cs+ reversibly inhibited (IC50, ≈1 mM) DAPs, and associated after‐discharges, that followed brief spike trains in each of sixteen cells tested. Although bath application of Cs+ also provoked a small reversible depolarization, inhibition of the DAP was retained when membrane voltage was kept constant by current injection.
Application of Cs+ had no significant effects on spike duration (n= 8), frequency‐dependent spike broadening (n= 8), spike hyperpolarizing after‐potentials (n= 14), or the amplitude of the isolated AHP (n= 7). Caesium‐evoked inhibition of the DAP, therefore, does not result from diminished spike‐evoked Ca2+ influx, and may reflect direct blockade of the conductance underlying the DAP.
Inhibition of the DAP was associated with an enhancement of the amplitude and duration of the AHP, indicating that the currents underlying the AHP and the DAP overlap in time following a train of action potentials, and that the relative magnitude of these currents is an important factor in determining the shape and time course of post‐train after‐potentials.
Bath application of Cs+ reversibly abolished phasic firing in each of seven cells tested. This effect was reversible and persisted at all subthreshold voltages tested. These results indicate that the current underlying the DAP is necessary for the genesis of plateau potentials and phasic firing in MNCs.
Effects of rapid shortening on rate of force regeneration and myoplasmic [Ca2+] in intact frog skeletal muscle fibres
Authors: Vandenboom R. , Claflin D. R. , Julian F. J. 
Published: September 2004

The effect of rapid shortening on rate of force regeneration (dF/dtR) was examined in single, intact frog (Rana temporaria) skeletal muscle fibres (3·0 °C). Step releases leading to unloaded shortening were applied after 500 ms of stimulation, during the plateau of an isometric tetanus. Initial mean sarcomere length ranged from 2·05 to 2·35 μm; force regeneration after shortening was at 2·00 μm.
Values for dF/dtR following a 25 nm half‐sarcomere−1 release were 3·17 ± 0·17 (mean ± s.e.m., n= 8) times greater than the initial rate of rise of force before release (dF/dtI). As release size was increased from 25 to 175 nm half‐sarcomere−1, the relationship between release size and dF/dtR decreased sharply before attaining a plateau value that was 1·34 ± 0·09 times greater than dF/dtI. Despite wide variations in dF/dtR, the velocity of unloaded shortening remained constant (2·92 ± 0·08 μm half‐sarcomere−1 s−1; n= 8) for the different release amplitudes used in this study.
To investigate its role in the attenuation of dF/dtR with increased shortening, the effects of rapid ramp (constant velocity) shortening on intracellular free Ca2+ concentration ([Ca2+]i) were monitored using the Ca2+‐sensitive fluorescent dye furaptra. Compared with an isometric contraction, rapid fibre shortening was associated with a transient increase in [Ca2+]i while force regeneration after shortening was associated with a transient reduction in [Ca2+]i. The greatest reductions in [Ca2+]i were associated with the largest amplitude ramps.
Cross‐bridge‐mediated modifications of the Ca2+ affinity of troponin C (TnC) may explain the fluctuations in [Ca2+]i observed during and after ramps. Associated fluctuations in TnC Ca2+ occupancy could play a role in the reduction of dF/dtR with increasing release size.
The transient outward current in mice lacking the potassium channel gene Kv1.4
Authors: London Barry , Wang Dao W. , Hill Joseph A. , Bennett Paul B. 
Published: September 2004

The transient outward current (Ito) plays a prominent role in the repolarization phase of the cardiac action potential. Several K+ channel genes, including Kv1.4, are expressed in the heart, produce rapidly inactivating currents when heterologously expressed, and may be the molecular basis of Ito.
We engineered mice homozygous for a targeted disruption of the K+ channel gene Kv1.4 and compared Ito in wild‐type (Kv1.4+/+), heterozygous (Kv1.4+/‐) and homozygous ‘knockout’ (Kv1.4−/−) mice. Kv1.4 RNA was truncated in Kv1.4−/− mice and protein expression was absent.
Adult myocytes isolated from Kv1.4+/+, Kv1.4+/− and Kv1.4−/− mice had large rapidly inactivating outward currents. The peak current densities at 60 mV (normalized by cellular capacitance, in pA pF−1; means ± s.e.m.) were 53.8 ± 5.3, 45.3 ± 2.2 and 44.4 ± 2.8 in cells from Kv1.4+/+, Kv1.4+/− and Kv1.4−/− mice, respectively (P < 0.02 for Kv1.4+/+vs. Kv1.4−/−). The steady‐state values (800 ms after the voltage clamp step) were 30.9 ± 2.9, 26.9 ± 3.8 and 23.5 ± 2.2, respectively (P < 0.02 for Kv1.4+/+vs. Kv1.4−/−). The inactivating portion of the current was unchanged in the targeted mice.
The voltage dependence and time course of inactivation were not changed by targeted disruption of Kv1.4. The mean best‐fitting V½ (membrane potential at 50 % inactivation) values for myocytes from Kv1.4 +/+, Kv1.4+/− and Kv1.4−/− mice were ‐53.5 ± 3.7, ‐51.1 ± 2.6 and ‐54.2 ± 2.4 mV, respectively. The slope factors (k) were ‐10.1 ± 1.4, ‐8.8 ± 1.4 and ‐9.5 ± 1.2 mV, respectively. The fast time constants for development of inactivation at ‐30 mV were 27.8 ± 2.2, 26.2 ± 5.1 and 19.6 ± 2.1 ms in Kv1.4+/+, Kv1.4+/− and Kv1.4−/− myocytes, respectively. At +30 mV, they were 35.5 ± 2.6, 30.0 ± 2.1 and 28.7 ± 1.6 ms, respectively. The time constants for the rapid phase of recovery from inactivation at ‐80 mV were 32.5 ± 8.2, 23.3 ± 1.8 and 39.0 ± 3.7 ms, respectively.
Nearly the entire inactivating component as well as more than 60 % of the steady‐state outward current was eliminated by 1 mm 4‐aminopyridine in Kv1.4+/+, Kv1.4+/− and Kv1.4−/− myocytes.
Western blot analysis of heart membrane extracts showed no significant upregulation of the Kv4 subfamily of channels in the targeted mice.
Thus, Kv1.4 is not the molecular basis of Ito in adult murine ventricular myocytes.
Role of myosin heavy chain composition in kinetics of force development and relaxation in rat myocardium
Authors: Fitzsimons Daniel P. , Patel Jitandrakumar R. , Moss Richard L. 
Published: September 2004

The effects of ventricular myosin heavy chain (MHC) composition on the kinetics of activation and relaxation were examined in both chemically skinned and intact myocardial preparations from adult rats. Thyroid deficiency was induced to alter ventricular MHC isoform expression from ∼80 %α‐MHC/20 %β‐MHC in euthyroid rats to 100 %β‐MHC, without altering the expression of thin‐filament‐associated regulatory proteins.
In single skinned myocytes, increased expression of β‐MHC did not significantly affect either maximal Ca2+‐activated tension (P0) or the Ca2+ sensitivity of tension (pCa50). However, unloaded shortening velocity (V0) decreased by 80 % due to increased β‐MHC expression.
The kinetics of activation and relaxation were examined in skinned multicellular preparations using the caged Ca2+ compound DM‐nitrophen and caged Ca2+ chelator diazo‐2, respectively. Myocardium expressing 100 %β‐MHC exhibited apparent rates of submaximal and maximal tension development (kCa) that were 60 % lower than in control myocardium, and a 2‐fold increase in the half‐time for relaxation from steady‐state submaximal force.
The time courses of cell shortening and intracellular Ca2+ transients were assessed in living, electrically paced myocytes, both with and without β‐adrenergic stimulation (70 nm isoproterenol (isoprenaline)). Thyroid deficiency had no affect on either the extent of myocyte shortening or the resting or peak fura‐2 fluorescence ratios. However, induction of β‐MHC expression by thyroid deficiency was associated with increased half‐times for myocyte shortening and relengthening and increased half‐time for the decay of the fura‐2 fluorescence ratio. Qualitatively similar results were obtained in both the absence and the presence of β‐adrenergic stimulation although the β‐agonist accelerated the kinetics of the twitch and the Ca2+ transient.
Collectively, these data provide evidence that increased β‐MHC expression contributes significantly to the observed depression of contractile function in thyroid deficient myocardium by slowing the rates of both force development and force relaxation.
Calcium cycling and contractile activation in intact mouse cardiac muscle
Authors: Gao Wei Dong , Perez Nestor Gustavo , Marban Eduardo 
Published: September 2004

Excitation‐contraction coupling in mouse cardiac muscle remains poorly characterized, despite the fact that the mouse is the mammalian species of choice for genetic manipulation. In this study, we characterized the relationship between internal calcium concentration ([Ca2+]i) and contraction in intact mouse ventricular muscle loaded with fura‐2 salt at 20–22°C.Both Ca2+transient amplitude and twitch force increased monotonically as external Ca2+concentration ([Ca2+]o) was increased up to 8.0 mm, with no changes in diastolic levels or in the times to peak of either Ca2+transients or force. The decay of Ca2+transients was accelerated as [Ca2+]oincreased, while relaxation was prolonged. Both Ca2+transient amplitude and twitch force increased as stimulation rate increased from 0.2 to 4 Hz, but the increase in force was much greater than the underlying increase in [Ca2+]i.The steady‐state force‐[Ca2+]irelationship revealed an [Ca2+]irequired for 50% of maximal activation (Ca50) of 0.95 ± 0.08 μm, a Hill coefficient of 9.9 ± 2.6, and a maximal Ca2+‐activated force (Fmax) of 60 ± 5 mN mm−2.Unlike rat ventricular myocardium, mouse cardiac muscle resists supraphysiological [Ca2+]o. The strong positive force‐frequency relationship in mouse cardiac muscle, with increases of force disproportionate to the increases in Ca2+transients, suggests frequency‐dependent ‘sensitization’ of the myofilaments. During steady‐state activation, mouse muscle exhibits decreased Ca2+responsiveness relative to other species, but high co‐operativity.These physiological features of mouse cardiac muscle merit consideration when interpreting the phenotypic consequences of genetic manipulations
Mathematical model of vertebrate gap junctions derived from electrical measurements on homotypic and heterotypic channels
Authors: Vogel Rolf , Weingart Robert 
Published: September 2004

A mathematical model has been developed which describes the conductive and kinetic properties of homotypic and heterotypic gap junction channels of vertebrates.
The model consists of two submodels connected in series. Each submodel simulates a hemichannel and consists of two conductances corresponding to a high (H) and low (L) conductance state and a switch, which simulates the voltage‐dependent channel gating.
It has been assumed that the conductances of the high state and low state vary exponentially with the voltage across the hemichannel.
The parameters of the exponentials can be derived from data of heterotypic or homotypic channels. As a result, the behaviour of heterotypic channels can be predicted from homotypic channel data and vice versa.
The two switches of a channel are governed by the voltage drop across the respective hemichannel. The switches of a channel work independently, thus giving rise to four conformational states, i.e. HH, LH, HL and LL.
The computations show that the dogma of a constant conductance for homotypic channels results from the limited physiological range of transjunctional voltages (Vj) and the kinetic properties of the channel, so a new fitting procedure is presented.
Simulation of the kinetic properties at the multichannel level revealed current time courses which are consistent with a contingent gating.
The calculations have also shown that the channel state LL is rare and of short duration, and hence easy to miss experimentally.
The design of the model has been kept flexible. It can be easily expanded to include additional features, such as channel substates or a closed state.
Demonstration of facilitatory I wave interaction in the human motor cortex by paired transcranial magnetic stimulation
Authors: Ziemann Ulf , Tergau Frithjof , Wassermann Eric M. , Wischer Stephan , Hildebrandt Jörg , Paulus Walter 
Published: September 2004

Transcranial magnetic stimulation (TMS) of the human motor cortex results in multiple discharges (D and I waves) in the corticospinal tract. We tested whether these volleys can be explored non‐invasively with paired TMS. The intensity of the first stimulus (S1) was set to produce a motor‐evoked potential (MEP) of 1 mV in the resting contralateral abductor digiti minimi (ADM) muscle; the second stimulus (S2) was set to 90 % of the resting motor threshold. At interstimulus intervals of 1·1‐1·5, 2·3‐2·9 and 4·1‐4·4 ms the MEP elicited by S1 plus S2 was larger than that produced by S1 alone.
Varying the S1 intensity between 70 and 130 % resting motor threshold with S2 held constant at 90 % resting motor threshold showed that the threshold for the first MEP peak was <= 70 % resting motor threshold. The second and third MEP peaks appeared only at higher S1 intensities. The latency of all peaks decreased with increasing S1 intensity.
Varying the S2 intensity with S1 held constant to produce a MEP of 1 mV on its own showed that the amplitude of all MEP peaks increased with S2 intensity, but that their timing remained unchanged.
Paired TMS in the active ADM (S1 clearly suprathreshold, S2 just above threshold; interstimulus interval, 1 ms) produced strong MEP facilitation. The onset of this facilitation occurred later by about 1·5 ms than the onset of the MEP evoked by S2 alone. No MEP facilitation was seen if the magnetic S2 was replaced by anodal or cathodal transcranial electrical stimulation.
It is concluded that the MEP facilitation after paired TMS, at least for the first MEP peak, is due to facilitatory interaction between I waves, and takes place in the motor cortex at or upstream from the corticospinal neurone.
Frequency‐dependent synaptic depression modifies postsynaptic firing probability in cats
Authors: Clark B. D. , Cope T. C. 
Published: September 2004

The influence of stimulus trains applied to single I a axons on the firing behaviour of single motoneurones was assessed in anaesthetized cats. The change in motoneurone firing probability associated with a single I a afferent spike was measured from short‐latency peaks in peristimulus time histograms or cross‐correlograms. Some synapses showed frequency‐dependent depression of the short‐latency peak, which is consonant with the frequency‐dependent depression reported for the I a‐motoneurone excitatory postsynaptic potential (EPSP).
Where they could be measured, EPSPs superimposed on the depolarizing ramps of potential recorded from motoneurones as they fired repetitively showed frequency‐dependent changes in amplitude that parallelled those of the simultaneously recorded histograms.
Thus it appears that at synapses with small EPSPs, which are typical in the mammalian CNS, modulation of the EPSP should result in similar modulation of cell firing.
Bilaterally evoked monosynaptic EPSPs, NMDA receptors and potentiation in rat sympathetic preganglionic neurones in vitro
Authors: Spanswick David , Renaud Leo P. , Logan Stephen D. 
Published: September 2004

Whole‐cell patch clamp and intracellular recordings were obtained from 190 sympathetic preganglionic neurones (SPNs) in spinal cord slices of neonatal rats. Fifty‐two of these SPNs were identified histologically as innervating the superior cervical ganglion (SCG) by the presence of Lucifer Yellow introduced from the patch pipette and the appearance of retrograde labelling following the injection of rhodamine‐dextran‐lysine into the SCG.
Electrical stimulation of the ipsilateral (n= 71) or contralateral (n= 32) lateral funiculi (iLF and cLF, respectively), contralateral intermediolateral nucleus (cIML, n= 41) or ipsilateral dorsal horn (DH, n= 34) evoked EPSPs or EPSCs that showed a constant latency and rise time, graded response to increased stimulus intensity, and no failures, suggesting a monosynaptic origin.
In all neurones tested (n= 60), fast rising and decaying components of EPSPs or EPSCs evoked from the iLF, cLF, cIML and DH in response to low‐frequency stimulation (0.03‐0.1 Hz) were sensitive to non‐NMDA receptor antagonists.
In approximately 50 % of neurones tested (n= 29 of 60), EPSPs and EPSCs evoked from the iLF, cLF, cIML and DH during low‐frequency stimulation were reduced by NMDA receptor antagonists. In the remaining neurones, an NMDA receptor antagonist‐sensitive EPSP or EPSC was revealed only in magnesium‐free bathing medium, or following high‐frequency stimulation.
EPSPs evoked by stimulation of the iLF exhibited a sustained potentiation of the peak amplitude (25.3 ± 11.4 %) in six of fourteen SPNs tested following a brief high‐frequency stimulus (10‐20 Hz, 0.1‐2 s).
These results indicate that SPNs, including SPNs innervating the SCG, receive monosynaptic connections from both sides of the spinal cord. The neurotransmitter mediating transmission in some of the pathways activated by stimulation of iLF, cLF, cIML and DH is glutamate acting via both NMDA and non‐NMDA receptors. Synaptic plasticity is a feature of glutamatergic transmission in some SPNs where EPSPs are potentiated following a brief high‐frequency stimulus. Our data also suggest a differential expression of NMDA receptors by these neurones.
Low‐conductance intercellular coupling between mouse chromaffin cells in situ
Authors: Moser Tobias 
Published: September 2004

Patch‐clamp experiments were used to compare membrane properties of mouse chromaffin cells in thin tissue slices and of isolated cells in primary culture. The mean membrane input resistance (Rin) and membrane capacitance were 3.1 ± 0.5 GΩ and 9.1 ± 0.5 pF in situ and 9.9 ± 1.8 GΩ and 8.2 ± 0.2 pF in isolated cells.
Spike‐like currents were observed on top of the calcium currents during depolarizations in thirty out of forty‐nine cells in situ. They were not seen in isolated cells nor after addition of Cd2+ (100 μM) and TTX (10 μM) to the perfusate of the slices. The mean Rin of cells which displayed current spikes (2.3 ± 0.18 GΩ) was significantly smaller than that of cells lacking spikes (3.9 ± 0.25 GΩ). It is suggested that the current spikes represent intercellular currents which result from action potential firing in neighbouring cells during the depolarization of the patch‐clamped cell.
Investigation of capacitative currents induced by square voltage pulses showed a slow component in twenty‐four out of twenty‐seven cells in situ.
It is concluded that a large fraction of mouse chromaffin cells in situ are electrically coupled. From the slow capacitative currents and the amplitude of the intercellular current spikes a junctional conductance between chromaffin cells of below 1 nS was deduced.
This junctional conductance appears to be too low to support spreading of electrical activity in cases where a single cell is stimulated by an action potential. However, the junctional conductance could allow longer depolarizations of one cell or simultaneous firing of several cells to trigger electrical activity in neighbouring cells.