Current Underlying (current + underlying)

Distribution by Scientific Domains

Selected Abstracts

A role for the volume regulated anion channel in volume regulation in the murine CNS cell line, CAD

V. L. Harvey
Abstract Aim:, The role of the volume regulated anion channel (VRAC) in a model CNS neuronal cell line, CAD, was investigated. Methods:, Changes in cell volume following hypotonic challenges were measured using a video-imaging technique. The effect of the Cl, channel antagonists tamoxifen (10 ,m) and 4,4,-diisothiocyanatostilbene-2,2,-disulphonic acid (DIDS; 100 ,m) on regulatory volume decrease (RVD) were measured. The whole-cell voltage-clamp technique was used to characterize IClswell, the current underlying the VRAC. Results:, Using the video-imaging technique, CAD cells were found to swell and subsequently exhibit RVD when subjected to a sustained hypotonic challenge from 300 mOsmol kg,1 H2O to 210 mOsmol kg,1 H2O. In the presence of tamoxifen (10 ,m) or DIDS (100 ,m) RVD was abolished, suggesting a role for the VRAC. A hypotonic solution (230 mOsmol kg,1 H2O) evoked IClswell, an outwardly rectifying current displaying time-independent activation, which reversed upon return to isotonic conditions. The reversal potential (Erev) for IClswell was ,14.7 1.4 mV, similar to the theoretical Erev for a selective Cl, conductance. IClswell was inhibited in the presence of DIDS (100 ,m) and tamoxifen (10 ,m), the DIDS inhibition being voltage dependent. Conclusions:, Osmotic swelling elicits an outwardly rectifying Cl, conductance in CAD cells. The IClswell observed in these cells is similar to that observed in other cells, and is likely to provide a pathway for the loss of Cl, which leads to water loss and RVD. As ischaemia, brain trauma, hypoxia and other brain pathologies can cause cell swelling, CAD cells represent a model cell line for the study of neuronal cell volume regulation. [source]

A modelling study of locomotion-induced hyperpolarization of voltage threshold in cat lumbar motoneurones

Yue Dai
During fictive locomotion the excitability of adult cat lumbar motoneurones is increased by a reduction (a mean hyperpolarization of ,6.0 mV) of voltage threshold (Vth) for action potential (AP) initiation that is accompanied by only small changes in AP height and width. Further examination of the experimental data in the present study confirms that Vth lowering is present to a similar degree in both the hyperpolarized and depolarized portions of the locomotor step cycle. This indicates that Vth reduction is a modulation of motoneurone membrane currents throughout the locomotor state rather than being related to the phasic synaptic input within the locomotor cycle. Potential ionic mechanisms of this locomotor-state-dependent increase in excitability were examined using three five-compartment models of the motoneurone innervating slow, fast fatigue resistant and fast fatigable muscle fibres. Passive and active membrane conductances were set to produce input resistance, rheobase, afterhyperpolarization (AHP) and membrane time constant values similar to those measured in adult cat motoneurones in non-locomoting conditions. The parameters of 10 membrane conductances were then individually altered in an attempt to replicate the hyperpolarization of Vth that occurs in decerebrate cats during fictive locomotion. The goal was to find conductance changes that could produce a greater than 3 mV hyperpolarization of Vth with only small changes in AP height (< 3 mV) and width (< 1.2 ms). Vth reduction without large changes in AP shape could be produced either by increasing fast sodium current or by reducing delayed rectifier potassium current. The most effective Vth reductions were achieved by either increasing the conductance of fast sodium channels or by hyperpolarizing the voltage dependency of their activation. These changes were particularly effective when localized to the initial segment. Reducing the conductance of delayed rectifier channels or depolarizing their activation produced similar but smaller changes in Vth. Changes in current underlying the AHP, the persistent Na+ current, three Ca2+ currents, the ,h' mixed cation current, the ,A' potassium current and the leak current were either ineffective in reducing Vth or also produced gross changes in the AP. It is suggested that the increased excitability of motoneurones during locomotion could be readily accomplished by hyperpolarizing the voltage dependency of fast sodium channels in the axon hillock by a hitherto unknown neuromodulatory action. [source]

Inhibition of slow Ca2+ -activated K+ current by 4-aminopyridine in rat hippocampal CA1 pyramidal neurones

Mogens Andreasen
The effect of 4-aminopyridine (4-AP) on the slow afterhyperpolarization (sAHP) seen after high frequency dendritic or somatic firing was investigated in rat hippocampal CA1 pyramidal neurones (PC). Intracellular recordings were obtained from the distal apical dendrites and somata and suprathreshold depolarizing current pulses were used to evoke a sAHP. The sAHP was blocked by low concentrations of carbacholine (Cch) but insensitive to high concentrations of apamin. In the presence of extracellular 4-AP, the first dendritic sAHP evoked was reduced compared to a maximal sAHP evoked in the absence of 4-AP. The reduction was evident at submillimolar concentration and increased to about 80% with 4 mM 4-AP. The stability of the 4-AP-induced block was affected by the type of anion used in the electrode solution. With K+ acetate (KAc) or K+ methylsulphate (KMeSO4) containing electrodes, the block was progressively removed during the initial 300 , 400 s of recordings. With KCl containing electrodes, the block remained stable and was 10% larger than that obtained with acetate. Detailed investigations showed that intracellular acetate promotes the removal of the 4-AP-induced block in an activity-dependent manner. Intracellularly applied 4-AP also induced an acetate-sensitive block of the dendritic sAHP. 4-AP also blocked the somatic sAHP and the stability of the block showed the same sensitivity towards anions as the dendritic sAHP. Thus 4-AP appears to block the slow Ca2+ -activated K+ current underlying the sAHP in a complex manner which is sensitive to certain types of anions. British Journal of Pharmacology (2002) 135, 1013,1025; doi:10.1038/sj.bjp.0704533 [source]

Ionic currents underlying rhythmic bursting of ventral mossy cells in the developing mouse dentate gyrus

Shozo Jinno
Abstract The electrophysiological properties of mossy cells were examined in developing mouse hippocampal slices using whole-cell patch-clamp techniques, with particular reference to the dorsoventral difference. Dorsal mossy cells exhibited a higher spontaneous excitatory postsynaptic potential (EPSP) frequency and larger maximal EPSP amplitude than ventral mossy cells. On the other hand, the blockade of synaptic inputs with glutamatergic and GABAergic antagonists disclosed a remarkable dorsoventral difference in the intrinsic activity: none (0/27) of the dorsal mossy cells showed intrinsic bursting, whereas the majority (35/47) of the ventral mossy cells exhibited intrinsic rhythmic bursting. To characterize the ionic currents underlying the rhythmic bursting of mossy cells, we used somatic voltage-clamp recordings in the subthreshold voltage range. Ventral bursting cells possessed both hyperpolarization-activated current (Ih) and persistent sodium current (INaP), whereas dorsal and ventral nonbursting cells possessed Ih but no INaP. Blockade of Ih with cesium did not affect the intrinsic bursting of ventral mossy cells. In contrast, the blockade of INaP with tetrodotoxin or phenytoin established a stable subthreshold membrane potential in ventral bursting cells. The current,voltage curve of ventral bursting cells showed a region of tetrodotoxin-sensitive negative slope conductance between ,55 mV and a spike threshold (, ,45 mV). On the other hand, no subthreshold calcium conductances played a significant role in the intrinsic bursting of ventral mossy cells. These observations demonstrate the heterogeneous electrophysiological properties of hilar mossy cells, and suggest that the subthreshold INaP plays a major role in the intrinsic rhythmic bursting of ventral mossy cells. [source]