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T C Pellmar

Publications and source records attributed to T C Pellmar.

At least 37 records · Page 2Linked to original sources
PubMed1990

Time- and dose-dependent changes in neuronal activity produced by X radiation in brain slices.

A new method of exposing tissues to X rays in a lead Faraday cage has made it possible to examine directly radiation damage to isolated neuronal tissue. Thin slices of hippocampus from brains of euthanized guinea pigs were exposed to 17.4 ke V X radiation. Electrophysiological recordings were made before, during, and after exposure to doses between 5 and 65 Gy at a dose rate of 1.54 Gy/min. Following exposure to doses of 40 Gy and greater, the synaptic potential was enhanced, reaching a steady level soon after exposure. The ability of the synaptic potential to generate a spike was reduced and damage progressed after termination of the radiation exposure. Recovery was not observed following termination of exposure. These results demonstrate that an isolated neuronal network can show complex changes in electrophysiological properties following moderate doses of ionizing radiation. An investigation of radiation damage directly to neurons in vitro will contribute to the understanding of the underlying mechanisms of radiation-induced nervous system dysfunction.

Action Potentials↗
PubMed1989

Free radicals mediate peroxidative damage in guinea pig hippocampus in vitro.

Previous studies have shown that peroxide caused electrophysiological damage. The present study investigates the action of agents that interfere with a free radical process in an effort to define the mechanism of peroxide damage. Deferoxamine chelates iron, making it unavailable for the Fenton reaction and thereby preventing the formation of hydroxyl free radicals from peroxide. Dimethylsulfoxide (DMSO) scavenges hydroxyl free radicals. Trolox-C, a water soluble Vitamin E analog, is an antioxidant that can scavenge peroxy radicals. Slices of hippocampus were removed from brains of euthanized guinea pigs. Electrical stimulation of an orthodromic pathway to CA1 region evoked a synaptic response and a population spike. Input-output curves were generated to evaluate the protection by deferoxamine, Trolox-C, and DMSO on the synaptic damage and impaired spike generation caused by peroxide. Lipid peroxidation was measured by the thiobarbituric acid test. Peroxide was found to increase lipid peroxidation. Deferoxamine and Trolox-C protected against the peroxide-induced synaptic damage, impaired spike generation, and lipid peroxidation. DMSO was ineffective synaptically but reduced peroxide damage to spike generating mechanisms and further lipid peroxidation. The data support the hypothesis that peroxide causes damage through a free radical mechanism.

Action Potentials↗
PubMed1989

A low-energy x-ray irradiator for electrophysiological studies.

A 50 kVp molybdenum target/filter x-ray tube has been installed inside a lead-shielded Faraday cage. High-dose rates of up to 1.54 Gy min-1 (17.4 keV weighted average photons) have been used to conduct local in vitro irradiations of the hippocampal region of guinea pig brains. Electrophysiological recordings of subtle changes in neuronal activity indicate this system is suitable for this application.

Animals↗
PubMed1989

Oxidative damage in the guinea pig hippocampal slice.

Free radicals and active oxygen compounds are implicated in brain ischemia and head trauma. Previous studies have shown that free radicals, generated by radiation and through the Fenton reaction, produce both synaptic and postsynaptic damage in the hippocampal brain slice. To evaluate the contribution of oxidation to the observed damage, the actions of the oxidants, chloramine-T and N-chlorosuccinimide (NCS), were studied on electrophysiological responses in the hippocampal slice isolated from the brains of guinea pigs. Electrical stimulation of afferents to neurons of the CA1 region of hippocampus evoked a population postsynaptic potential (population PSP) in the dendritic layer and a population spike in the cell body layer. Chloramine-T (25-500 microM) and NCS (750-4000 microM) decreased the population spike in a dose-dependent manner (ED50 congruent to 125 microM and 1100 microM, respectively). Input/output curves revealed that both the population PSP were significantly reduced with both oxidants; but, the ability of the population PSP to produce a population spike was not impaired. These studies suggest that oxidation reactions can account for the synaptic component of the damage produced by free radicals but can not account for the postsynaptic effects.

Animals↗
PubMed1988

Effects of dithiothreitol, a sulfhydryl reducing agent, on CA1 pyramidal cells of the guinea pig hippocampus in vitro.

The radioprotectant, dithiothreitol (DTT) has been shown to increase excitability in the hippocampal slice preparation. In the present study, intracellular recording techniques were used to further examine the actions of DTT. Electrophysiological recordings from CA1 pyramidal cells were obtained prior to, during and after DTT exposure. DTT caused a small depolarization without altering membrane resistance. DTT induced spontaneous firing and occasional burst firing in normally silent neurons. These effects were accompanied by a reduction in spike frequency adaptation but no change in the afterhyperpolarization following a train of action potentials. Following DTT exposure, orthodromic stimulation produced multiple firing. Subthreshold excitatory postsynaptic potentials (EPSPs) were significantly prolonged. Isolating the CA1 subfield, attenuated the prolongation of the EPSP by DTT. Recurrent inhibitory postsynaptic potentials were unaffected by DTT. The actions of DTT are likely to result from DTT-induced reduction of disulfide bonds since the reduced form of DTT does not cause a similar hyperexcitability.

Action Potentials↗
PubMed1987

Dithiothreitol elicits epileptiform activity in CA1 of the guinea pig hippocampal slice.

Dithiothreitol (DTT) is a sulfhydryl reducing agent used as a radioprotectant. Exposure of hippocampal slices for 30 min to 0.5 mM DTT irreversibly increased the orthodromic population spike amplitude, promoted repetitive firing and induced spontaneous epileptiform activity in the CA1 subfield. The same concentration of the oxidized form of DTT did not increase hippocampal excitability. Although the slope of the population synaptic response to afferent stimulation (popPSP) was unchanged by DTT, the duration of the popPSP was prolonged. Recurrent inhibition was unaffected. DTT probably exerts its effects through an irreversible chemical reaction with cellular components. Possible mechanisms of DTT-induced epileptiform activity are discussed.

Animals↗
PubMed1987

Peroxide alters neuronal excitability in the CA1 region of guinea-pig hippocampus in vitro.

Effects of peroxidative damage on neuronal excitability were investigated with electrophysiological techniques in CA1 pyramidal cells of the hippocampal slice preparation. Hydrogen peroxide alone or combined with ferrous ions (peroxide/iron) is likely to produce hydroxyl free radicals through the Fenton reaction. Intracellularly recorded excitatory postsynaptic potentials and inhibitory postsynaptic potentials were significantly reduced by exposure to peroxide, while responses to iontophoretically applied GABA and glutamate were unaffected. These results suggest that peroxide has presynaptic actions. Peroxide and peroxide/iron also increased frequency adaptation; after exposure, neurons fired fewer action potentials at a lower frequency in response to the same depolarizing current step. A voltage clamp analysis revealed that the potassium currents were unaffected by peroxide/iron. Calcium current was not obviously altered by exposure to peroxide. Sodium spike threshold was also unaffected. Calcium spike threshold was significantly increased by peroxide. This action of peroxide may underlie its presynaptic actions. It is concluded that peroxide produces both presynaptic and postsynaptic damage. This damage is likely to result from the production of free radicals which have been postulated to underlie a number of pathological states.

Action Potentials↗
PubMed1987

Ionizing radiation alters neuronal excitability in hippocampal slices of the guinea pig.

To investigate the effects of ionizing radiation on an isolated neuronal network without complicating systemic factors, slices of hippocampus from the guinea pig were isolated and studied in vitro. Slices were irradiated with a 60Co source and compared to paired, sham-irradiated controls. Electrophysiological activity in the CA 1 population of pyramidal cells was evoked by stimulation of the stratum radiatum. Analysis of the somatic and dendritic responses suggested sites of radiation damage. Orthodromically evoked activity was significantly decreased in slices receiving greater than 75 Gy gamma radiation. The effects were dose and dose-rate dependent. At 20 Gy/min, doses of 50 Gy and greater produced synaptic impairment while doses of 75 Gy and greater also produced postsynaptic damage (i.e., the ability of the synaptic response to generate an action potential). A lower dose rate, 5 Gy/min, reduced the sensitivity of synaptic damage to radiation exposure; synaptic impairment required a dose of 100 Gy or greater at the lower dose rate. In contrast, postsynaptic damage was not sensitive to dose rate. This study demonstrates that ionizing radiation can directly affect the integrated functional activity of neurons.

Animals↗
PubMed1986

Resistance of afterhyperpolarizations in hippocampal pyramidal cells to prostaglandins and vasoactive intestinal polypeptide (VIP).

The afterhyperpolarization (AHP) that follows repetitive stimulation was recorded intracellularly from CA1 pyramidal neurons in the guinea pig hippocampal slice preparation. Although the late AHP could be blocked by histamine (1-10 microM), forskolin (10 microM) and 8-bromo-cyclic AMP (100 and 500 microM), neither prostaglandins D2, E1 and F2 alpha (0.5 microM) nor vasoactive intestinal polypeptide (0.5 microM) had any effect on the AHP, membrane potential, membrane resistance or action potential properties.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1986

Histamine decreases calcium-mediated potassium current in guinea pig hippocampal CA1 pyramidal cells.

The action of histamine on CA1 pyramidal cells was studied in a hippocampal slice preparation. In the presence of tetrodotoxin (TTX) and tetraethylammonium (TEA), histamine had little effect on the calcium spikes. Using the single-electrode voltage-clamp technique, the actions of histamine on membrane currents were tested. In TTX, histamine (1 microM) decreased outward current only at potentials more depolarized than approximately -50 mV, where calcium-mediated potassium current is predominant. In the presence of manganese, histamine was without effect. Histamine (10 microM) did not affect the transient outward potassium current (A-current), the inward M-current resulting from small hyperpolarizing steps, or the inward Q-current elicited by larger hyperpolarizing steps. Blocking potassium currents with TEA or replacing calcium with barium revealed a slow inward current normally carried by calcium. With TTX present to block sodium currents, histamine (10 microM) did not reduce the inward current. The outward current reduced by a maximally effective concentration of histamine (10 microM) can be further decreased by manganese. The results support the conclusion that histamine selectively decreases the calcium-mediated potassium conductance in CA1 pyramidal cells of hippocampus. The possibility is raised that there is a component of calcium-mediated potassium current that is insensitive to histamine.

Animals↗
PubMed1984

Enhancement of inward current by serotonin in neurons of Aplysia.

In RB cells of Aplysia, serotonin, in the presence of TEA, 4AP and Ba, elicits a voltage-dependent inward current. In Ba-TEA-4AP seawater, RB cells showed a negative slope region (NSR) in their current-voltage (I-V) relationship when measured at the end of 2-s commands from a holding potential of -60 mV. Addition of serotonin to the bathing solution enhanced the NSR. When holding potential was lowered to -10 mV, the NSR as well as the effects of serotonin were greatly reduced. Addition of 20 mM cobalt to the bathing solution blocked both the NSR and the inward current produced by serotonin. Changes in potassium concentration produced no consistent shift in voltage sensitivity nor change in amplitude of the current elicited by serotonin. Intracellular injection of cesium sufficient to broaden action potentials did not block the enhancement of NSR by serotonin. These results support the conclusion that in RB cells, serotonin produces a voltage-dependent current carried by calcium ions.

Animals↗
PubMed1981

Voltage-dependent current evoked by dopamine and octopamine in Aplysia.

Octopamine and dopamine evoke a slow voltage-dependent inward current in neurons of Aplysia. The responses are present only at depolarized potentials (greater than -40 mV). They are insensitive to changes in potassium, persist after removal of sodium, are not reduced by low chloride solution, and are blocked by cadmium. Because of the similarities in voltage-dependence, time course and ionic sensitivities, the ionic mechanism of the voltage-dependent responses to octopamine and dopamine are concluded to be the same as that of the voltage-dependent response to serotonin reported previously.

Animals↗
PubMed1981

Cyclic AMP induces a voltage-dependent current in neurones of Aplysia californica.

A voltage-dependent inward current is elicited by intracellular application of cyclic AMP in some neurons of Aplysia. The current has a slow time course and is present only at potentials more depolarized than -30 mV. Two other methods of increasing cellular cyclic AMP (phosphodiesterase inhibitors and sodium fluoride activation of adenylate cyclase) also induce an inward current at depolarized potentials.

Animals↗
PubMed1981

Effects of furosemide on neural mechanisms in Aplysia.

The effects of furosemide on action potentials and responses to several neurotransmitters have been studied in the neurons of Aplysia. Furosemide (10(-7) and 10(-3) M) does not visibly affect the normal action potential in R15 neurons. However, when TTX (30 microM) is used to block the sodium component in R15, the remaining spike (presumably the calcium component) is increased in amplitude in the presence of furosemide. Furosemide also alters transmitter-induced conductances. Furosemide greatly reduces the amplitude and shifts, in a depolarizing direction, the reversal potential of chloride-dependent responses to gamma-aminobutyric acid (GABA) and acetylcholine (ACh). This suggests that furosemide both blocks the chloride channel and inhibits a chloride pump. ACh-induced sodium responses were also reduced by furosemide but to a lesser extent than chloride responses. The potassium response to ACh and a voltage-dependent calcium response to serotonin were not altered. These results indicate that furosemide could alter synaptic responses both presynaptically by enhancement of calcium flux during the action potential and postsynaptically by blockade of chloride and sodium conductances.

Acetylcholine↗
PubMed1981

Ionic mechanism of a voltage-dependent current elicited by cyclic AMP.

Intracellular pressure injection of cyclic AMP induces a slow voltage-dependent inward current in some neurons of Aplysia californica. The time course, voltage dependence, and ionic sensitivities of this response are nearly identical to those of the voltage-dependent calcium current induced by serotonin in the same preparation. The response to cyclic AMP is unaffected by changes in the extracellular concentration of chloride or potassium. The current is slowly but minimally reduced by a sodium-free solution. The calcium channel blocker, cadmium, blocks the current elicited by injection of cyclic AMP. The data presented here suggest that cyclic AMP can induce a voltage-dependent calcium current.

Animals↗
PubMed1981

Does cyclic 3' ,5'-adenosine monophosphate act as second messenger in a voltage-dependent response to 5-hydroxytryptamine in Aplysia?

1 The possibility that cyclic adenosine 3',5'-monophosphate (cyclic AMP) mediates a voltage-dependent inward current elicited by 5-hydroxytryptamine (5-HT) in RB and LB cells of the abdominal ganglion of Aplysia was tested. 2 Intracellular injection of cyclic AMP elicited an inward current with a similar time course, potential dependence and ionic sensitivity as the response to 5-HT. 3 Intracellular injection of guanylyl imidodiphosphate (GMP-PNP), which activated adenylate cyclase, neither mimicked nor enhanced the 5-HT-evoked current. On the contrary, it reduced the current. 4 The phosphodiesterase inhibitors, Ro20-1724, isobutyl methylxanthine (IBMX) and theophylline, each antagonized the voltage-dependent response to 5-HT. To varying degrees they each induced an inward current. 5 The adenylate cyclase antagonist, dithiobisnitrobenzoic acic (DTNB), had no effect on the response to 5-HT when applied either intracellularly or extracellularly. Intracellular injection of the phosphodiesterase activator imidazole also had no effect. 6 Tubocurarine and neostigmine did not reduce the voltage-dependent inward current evoked by 5-HT; methysergide elicited an inward current. 7 Although the observations that cyclic AMP and 5-HT can evoke similar voltage-dependent inward currents in RB and LB neurones of Aplysia might suggest a second messenger role for the cyclic nucleotide, the pharmacological data are inconsistent with this hypothesis.

1-Methyl-3-isobutylxanthine↗
PubMed1981

Transmitter-induced calcium current.

Iontophoretic application of serotonin on some neurons of Aplysia causes a slow, voltage-dependent inward current. Experimental evidence indicates that the current is carried by calcium ions: the response to serotonin is unaffected by changes in chloride or potassium concentration, slowly attenuated by sodium-free solutions, reduced in some (although not all) preparations by a low-calcium solution, and blocked by calcium channel blockers. The transmitter-induced calcium current has a voltage sensitivity similar to that of calcium currents in other systems. Intracellular application of cyclic AMP also elicits a voltage-dependent inward current. Although cyclic AMP mimics serotonin, pharmacological agents do not have the actions expected if cyclic AMP were mediating the response to serotonin, Phosphodiesterase inhibitors block the responses to both serotonin and cyclic AMP; 5,5'-dithiobis(2-nitrobenzoic acid), and adenylate cyclase inhibitor, and imidazole, a phosphodiesterase activator, do not reduce the serotonin response. Because calcium has many important roles in neuronal activity, including synaptic transmission, the current evoked by serotonin and by cyclic AMP, whether acting independently or as part of the same mechanism, would have important functional consequences.

Animals↗