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T J Blaxter

Publications and source records attributed to T J Blaxter.

8 recordsLinked to original sources
PubMed1989

Pharmacological and anatomical separation of calcium currents in rat dentate granule neurones in vitro.

1. Rat dentate granule neurones in hippocampal slices were voltage-clamped at 21-23 degrees C using CsCl-filled microelectrodes. The perfusate contained TTX and K+ channel blockers to isolate pharmacologically inward Ca2+ currents. 2. From hyperpolarized holding potentials of -65 to -85 mV, depolarizing test potentials to between -50 and -40 mV elicited a transient (100-200 ms) low-threshold (TLT) current which was also elicited from more depolarized holding potentials following hyperpolarizing voltage steps of -40 mV or greater. 3. Larger depolarizing steps from a hyperpolarized holding potential triggered a large (2-6 nA), transient high-threshold (THT) inward current, rapidly peaking and decaying over 500 ms, followed by a sustained inward current component. 4. At depolarized holding potentials (-50 to -20 mV), the THT current was apparently inactivated and a sustained high-threshold (SHT) inward current was evident during depolarizing voltage steps of 10 mV or more. 5. From hyperpolarized holding potentials with depolarizing voltage steps of 10-30 mV, most neurones demonstrated a small-amplitude, sustained low-threshold (SLT) inward current with similar characteristics to the SHT current. 6. Zero-Ca2+ perfusate or high concentrations of Ca2+ channel blockers (Cd2+, Mn2+ or Ni2+) diminished or abolished all inward currents. 7. Repetitive voltage step activation of each current at 0.5 Hz reduced the large THT current to less than 25% of an unconditioned control current, reduced the SHT current by 50%, but had little effect on the TLT current. 8. A low concentration of Cd2+ (50 microM) blocked the THT and SHT currents with little effect on the TLT current. Nimodipine (1 microM) attenuated the SHT current. Ni2+ (100 microM) selectively attenuated the TLT current. 9. In low-Ca2+ perfusate, high concentrations of Ca2+ (10-15 mM), focally applied to different parts of the neurone, increased the THT current when applied to the dendrites, the SHT current when applied to the soma and the TLT current at all locations. Conversely, in regular perfusate, Cd2+ (1-5 mM), focally applied to the dendrites decreased the THT current and somatic applications decreased the SHT current. The TLT current was diminished regardless of the site of Cd2+ application. 10. These results suggest the existence of three different Ca2+ currents in dentate granule cells separable by their activation and inactivation characteristics, pharmacology and site of initiation.

Animals↗
PubMed1988

Measurements of dendritic conductance changes to GABA in granule cells of the rat dentate gyrus.

The magnitude of dendritic conductance changes occurring distantly from the somatic site of recording can be difficult to measure. We have used measurements of the neuronal time constant, tau 0, instead of the neuronal input resistance, RN, to estimate the resistance decrease that accompanies the depolarizing response of the dendrites of granule cells when GABA is applied. From the changes in tau 0, we estimated the reversal potential of the response and found that the conductance change accompanying a given GABA-mediated voltage response as measured at the cell body was the same regardless of where in the dendritic tree the drug was applied. On the other hand, RN changes underestimated the increase in conductance of the GABA responses in the distal dendrites and were not accurate for determining the reversal potential.

Algorithms↗
PubMed1988

GABA responses in rat dentate granule neurons are mediated by chloride.

The dendrites of granule cells in hippocampal slices responded to gamma-aminobutyric acid (GABA) with a depolarization. The response was blocked by picrotoxin in a noncompetitive manner. Reductions in the extracellular chloride ion concentration changed the reversal potential of the response by an amount predicted from the Nernst equation for chloride ion. Chloride-dependent hyperpolarizing responses were sometimes also found in the cell body of the granule cells. Since the reversal potential followed that predicted from the Nernst equation for chloride, we conclude that the response was mediated by chloride ions alone with no contribution from other ions. This has not previously been shown for the depolarizing response to GABA in central neurons.

Animals↗
PubMed1986

gamma-Aminobutyric acid hyperpolarizes rat hippocampal pyramidal cells through a calcium-dependent potassium conductance.

Application of gamma-aminobutyric acid (GABA) to the dendrites of CA1 pyramidal cells in hippocampal slices produced depolarizing and hyperpolarizing responses. Picrotoxin (50 microM) blocked the depolarizing response of the dendrites to GABA but not the hyperpolarizing responses of the dendrites. The hyperpolarizing response of the cell body to GABA was reduced but not blocked by picrotoxin, suggesting the presence of a complex response at the cell body. The depolarizing response of the dendrites and the hyperpolarizing response of the cell body appeared to be at least partly Cl- dependent as they were respectively increased and decreased in size in low-Cl- artificial cerebrospinal fluid (ACSF), while the hyperpolarizing response of the dendrites was unaffected. The hyperpolarizing response of the dendrites was increased in amplitude in low-K+ ACSF and the extrapolated reversal potential of the response became more negative, suggesting that the response was K+ dependent. The hyperpolarizing response of the dendrites was decreased in size in high-K+ ACSF and could be readily inverted by current injection. The reversal potential became less negative in high-K+ ACSF in a similar manner to that of the slow after-hyperpolarization following a train of spikes, indicating that the response was a K+ conductance. Perfusion of the slice with normal or 0-Ca2+ ACSF containing Cd2+ or Mn2+ blocked synaptic transmission, increased spike duration and blocked the slow phase of the spike after-hyperpolarization (a.h.p.). This latter potential is thought to be mediated by a Ca2+-dependent K+ conductance. Later, the hyperpolarizing response of the dendrites to GABA was blocked without an effect on the other GABA responses. Pressure application of Cd2+ (0.2-2 mM) onto the surface of the slice rapidly reduced or blocked the slow a.h.p. and the dendritic hyperpolarizing response to GABA. Intracellular injection of EGTA rapidly blocked the slow phase of the a.h.p. and then later blocked or reduced the dendritic hyperpolarizing response to GABA. We conclude that the hyperpolarizing response of the dendrites to GABA is mediated by a Ca2+-dependent K+ conductance.

Action Potentials↗
PubMed1985

Pre- and postsynaptic effects of baclofen in the rat hippocampal slice.

CA1 pyramidal cells responded to baclofen with a hyperpolarization. This response was found in the apical and basal dendrites and, like the hyperpolarizing response of the dendrites to GABA, appeared to be Ca2+-dependent since it was blocked or reduced by intracellular injection of EGTA or extracellular application of cadmium. Baclofen also reduced the excitatory and inhibitory postsynaptic potentials produced by stimulation of the Schaffer collaterals. The pre- and postsynaptic effects on the synaptic waveform could be distinguished.

Animals↗
PubMed1985

Actions of GABA and ethylenediamine on CA1 pyramidal neurones of the rat hippocampus.

The effects of locally applied gamma-aminobutyric acid (GABA) and ethylenediamine were examined and compared on CA1 pyramidal neurones in slice preparations of rat hippocampus using intracellular voltage recording techniques. Each substance produced both depolarization and hyperpolarization of the dendrites; the cell body responded with hyperpolarization alone. Ion substitution experiments suggest that the depolarizing responses of the dendrites were Cl- dependent and the hyperpolarizing responses of the cell body were dependent on Cl-, which suggests that the Cl- potential (EC1) is different in the dendrites compared with the cell body. The hyperpolarizing responses of the dendrites were dependent on K+. Dendritic depolarizing responses to GABA and ethylenediamine were antagonized by bicuculline and picrotoxin whereas the dendritic hyperpolarizing response was unaffected. The hyperpolarizing responses of the cell body were more difficult to study but it appeared that they were reduced by both bicuculline and picrotoxin. The benzodiazepines flurazepam and diazepam potentiated the dendritic depolarizing responses to GABA and ethylenediamine. It also had this effect on the hyperpolarizing response of the cell body but not on the hyperpolarizing response of the dendrites.

Animals↗
PubMed1985

Enhanced neuronal K+ conductance: a possible common mechanism for sedative-hypnotic drug action.

It is commonly thought that central nervous system depressant drugs exert their actions through enhancement of gamma-aminobutyrate (GABA)-mediated mechanisms. Recently, the cellular electrophysiological evidence from this laboratory and others suggests that both sedative hypnotics and general anaesthetics inhibit central neurons by increasing potassium conductance (GK). We have utilized the mammalian in vitro hippocampal and cerebellar slice preparations at 34-36 degrees C. Intracellular recordings from CA1, CA3, and cerebellar Purkinje cells were obtained. Low dose (sedative) concentrations of ethanol (less than or equal to 20 mM), two different benzodiazepines (midazolam and clonazepam in low nanomolar concentrations), and pentobarbital (10(-6) to 10(-4) M) were applied by pressure ejection or were bath perfused. All drugs caused a hyperpolarization with decreased spontaneous activity, and enhanced post spike afterhyperpolarizations (AHPs). These long-lasting AHPs are presumably due to enhanced calcium-mediated GK. Increased responsiveness to focally applied GABA was only seen at higher doses (ethanol, 100 mM; midazolam, 10(-7) M; pentobarbital, 10(-4) M). These data suggest that the above neurodepressant drugs, when applied at sedative doses to hippocampal pyramidal cells, enhance GK and not the actions of GABA.

Animals↗