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D V Madison

Publications and source records attributed to D V Madison.

46 records · Page 3Linked to original sources
PubMed1986

Cyclic adenosine 3',5'-monophosphate mediates beta-receptor actions of noradrenaline in rat hippocampal pyramidal cells.

Intracellular recordings were made from rat hippocampal CA1 pyramidal neurones in the in vitro slice preparation to study the actions of cyclic adenosine 3',5'-monophosphate (cyclic AMP). Application of the membrane permeant analogue of cyclic AMP, 8-Br cyclic AMP caused a small depolarization of the resting membrane potential accompanied by an increase in membrane input resistance and also reduced the amplitude of depolarization-evoked calcium-activated potassium after-hyperpolarizations (a.h.p.s.). 8-Br cyclic AMP reduced calcium-activated a.h.p.s but did not reduce calcium action potentials in these cells. 8-Br cyclic AMP also reduced action potential frequency accommodation. The effects of 8-Br cyclic AMP were not mimicked by cyclic AMP applied extracellularly but were imitated by intracellular injections of cyclic AMP. Activation of the endogenous adenylate cyclase of pyramidal cells either by intracellular injection of the stable guanosine 5'-triphosphate (GTP) analogue guanylyl-imidodiphosphate, or by extracellular application of forskolin, reduced the a.h.p. and accommodation. Reducing phosphodiesterase activity with application of either 3-isobutyl-1-methylxanthine or Ro20-1724 reduced the amplitude of the a.h.p. and potentiated the a.h.p.-blocking action of noradrenaline. Reducing adenylate cyclase activity by application of SQ22,536 slightly increased the amplitude of the (a.h.p.) and reduced the a.h.p.-blocking action of noradrenaline. We conclude that the beta-receptor actions of NA on hippocampal CA1 pyramidal cells are mediated by intracellularly produced cyclic AMP.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Phorbol esters mimic some cholinergic actions in hippocampal pyramidal neurons.

Muscarinic receptor stimulation in the hippocampus has been associated with inositol phospholipid breakdown. In other systems this leads to the formation of inositol trisphosphate and diacylglycerol, which promotes the activation of protein kinase C. Phorbol esters, which directly activate protein kinase C, exhibit high and specific binding in the hippocampus. This, along with the advantages of the hippocampal slice preparation, including direct pharmacological access to a cell population (CA1 pyramidal cells) having clearly defined muscarinic responses, makes this an ideal preparation to examine whether protein kinase C serves as the intracellular signal for muscarinic receptor occupation. Like muscarinic agonists, phorbol esters abolish the slow calcium-activated potassium afterhyperpolarizing potential (AHP) and its underlying current without reducing calcium action potentials. Those phorbol analogs that do not activate kinase C have no effect, suggesting that activation of this enzyme is required to reduce the AHP. The accommodation of spike discharge normally seen during a long depolarizing stimulus is also markedly reduced by phorbol esters as well as by muscarinic receptor activation. However, unlike muscarinic agonists, phorbol esters have no effect on the muscarine-sensitive, voltage-dependent, potassium current termed IM, nor do they consistently cause an increase in input resistance. Moreover, unlike ACh, they do not appear to have a presynaptic inhibitory action on the fast EPSP elicited by orthodromic stimulation. The slow cholinergic EPSP was blocked by phorbol esters, but this could be accounted for by a postsynaptic action. Thus, if inositol phospholipid turnover is involved in mediating muscarinic responses in the hippocampus, the activation of protein kinase C can account for only part of the electrophysiological response.

Acetylcholine↗
PubMed1985

Folic acid has a disinhibitory action in the rat hippocampal slice preparation.

The effects of folic acid on synaptic transmission in the hippocampal slice have been studied. Application of folic acid (0.1-1 mM) increased the size of population spikes recorded extracellularly in the CAl pyramidal cell layer and caused the appearance of multiple population spikes. Intracellular recording revealed that folic acid had no consistent effect on the membrane potential, but greatly reduced the rapid chloride-mediated phase of the inhibitory postsynaptic potential (IPSP) evoked by ortho- and antidromic stimulation. The slower, potassium-mediated phase of the IPSP was usually enhanced. Furthermore, folic acid abolished spontaneous IPSPs recorded with potassium chloride-filled microelectrodes. All of these effects were quickly reversible when the drug was washed from the chamber. Finally bath-applied folic acid reduced the hyperpolarization produced by iontophoretically applied GABA. Based on these results, we conclude that folic acid produces its excitatory effects on hippocampal pyramidal cells by a disinhibitory action which involves a postsynaptic blockade of GABA responses.

Animals↗
PubMed1984

Control of the repetitive discharge of rat CA 1 pyramidal neurones in vitro.

Experiments using intracellular recording techniques were performed on rat hippocampal neurones in vitro, to study the discharge properties of these cells. When CA 1 pyramidal cells were excited by injecting long depolarizing current pulses (approximately 600-800 ms), they responded with an initial rapid action potential discharge which slowed, or accommodated, and then stopped after 200-300 ms. The train of action potentials was followed by a hyperpolarization which was due primarily to calcium-activated potassium conductance (GK(Ca]. The amplitude of this hyperpolarization increased with an increasing number of action potentials in the initial discharge. Blocking the calcium-activated potassium conductance, by injecting EGTA into the cell, by bathing the cell in cadmium, a calcium channel blocker, or by bathing the cell in calcium-free medium, reduced the after-hyperpolarization (a.h.p.) and accommodation such that the frequency of action potential discharge increased and the duration of this discharge was prolonged. Blocking the calcium-activated potassium conductance had a greater effect on discharge frequency later in the action potential train, as late interspike intervals were shortened more than early ones by the application of cadmium or of calcium-free medium. This was presumably because the calcium-activated potassium conductance was more developed later in the train. Accommodation was not completely abolished in the absence of calcium and presence of cadmium, suggesting that other factors, in addition to calcium-activated potassium conductance, contributed to this process. This remaining accommodation was reduced by low doses of carbachol, suggesting that the M-current also plays a role in accommodation. We conclude that accommodation of the action potential discharge of hippocampal pyramidal cells may be regulated by at least two potassium currents: the calcium-activated potassium current and the M-current. Both of these currents are turned on during excitation of the neurone and act in an inhibitory manner on that neurone to limit further action potential discharge.

Action Potentials↗
PubMed1982

General anesthetics hyperpolarize neurons in the vertebrate central nervous system.

The effect of general anesthetics on frog motoneurons and rat hippocampus pyramidal cells was examined with sucrose gap and intracellular recording, respectively. A number of volatile and intravenous anesthetics directly hyperpolarized the motoneurons. The potency of these agents in hyperpolarizing motoneurons was strongly correlated with their anesthetic potency. While the responses to barbiturates and alpha-chloralose were blocked by gamma-aminobutyric acid antagonists and were dependent on the chloride gradient, the responses to all the other anesthetics tested were generated by a separate mechanism. Intracellular recording from hippocampal pyramidal cells suggested that an increase in potassium conductance accounts for these responses. Such a nonsynaptic action would contribute to the decreased neuronal responsiveness observed for these compounds and thus to their anesthetic action.

Anesthetics↗
PubMedDate not supplied

Potentiation of synaptic transmission in the hippocampus by phorbol esters.

Protein kinase C (PKC), a calcium-dependent phospholipid-sensitive kinase which is selectively activated by phorbol esters, is thought to play an important role in several cellular processes. In mammalian brain PKC is present in high concentrations and has been shown to phosphorylate several substrate phosphoproteins, one of which may be involved in the generation of long-term potentiation (LTP), a long-lasting increase in synaptic efficacy evoked by brief, high-frequency stimulation. Since the hippocampus contains one of the brain's highest levels of binding sites for phorbol esters and is the site where LTP has been most thoroughly characterized, we examined the effects of phorbol esters on hippocampal synaptic transmission and LTP. We found that phorbol esters profoundly potentiate excitatory synaptic transmission in the hippocampus in a manner that appears indistinguishable from LTP. Furthermore, after maximal synaptic enhancement by phorbol esters, LTP can no longer be elicited. Although the site of synaptic enhancement during LTP is not clearly established, phorbol esters appear to potentiate synaptic transmission by acting primarily at a presynaptic locus since changes in the postsynaptic responses to the putative transmitter, glutamate, cannot account for the increased synaptic responses induced by phorbol esters. These findings, in conjunction with previous biochemical studies, raise the possibility that, in mammalian brain, PKC plays a role in controlling the release of neurotransmitter and may be involved in the generation of LTP.

Animals↗
PubMedDate not supplied

Phorbol esters block a voltage-sensitive chloride current in hippocampal pyramidal cells.

The importance of second-messenger systems in controlling the excitability of neurones and other cells, through modulation of voltage- and calcium-dependent ionic conductances, has become increasingly clear. Cyclic AMP, acting via protein kinase A, has been identified as the second messenger for several neurotransmitters, and recent studies have suggested that activation of protein kinase C may have similar modulatory actions on neurones. Calcium and potassium currents have so far been shown to be the major ionic conductances modified by kinase activation. We now report that hippocampal pyramidal cells contain a previously undescribed voltage-dependent chloride current which is active at resting potential and is turned off either by membrane depolarization or by activation of protein kinase C by phorbol esters. We propose that this current may reside predominantly in the cell's dendritic membrane and thereby may regulate dendritic excitability.

Animals↗
PubMedDate not supplied

Basal and apical synapses of CA1 pyramidal cells employ different LTP induction mechanisms.

Nitric oxide (NO) production has been widely reported to be required for the induction of long-term potentiation (LTP) in hippocampal CA1 cells. Of the two constitutive isoforms of NO synthase, the endothelial form (eNOS) has been implicated in the induction of LTP in these cells. The distribution of eNOS within CA1 cells is not uniform, however, being present in the cell bodies and apical dendrites but absent from the basal dendrites. Using extracellular and intracellular recording techniques, we demonstrate that LTP induction in stratum radiatum synapses (onto apical dendrites) is dependent on NO production, being attenuated by pretreatment with a NOS inhibitor. LTP induced in stratum oriens synapses (onto basal dendrites) is, however, resistant to NOS inhibitors. Both forms of LTP require the activation of N-methyl-D-aspartate (NMDA) receptors because induction of LTP in both stratum radiatum and stratum oriens is blocked by AP5. Thus, it appears that synapses onto apical and basal dendrites of CA1 cells use different cellular mechanisms of LTP induction.

Animals↗