Physical and physiological characteristics of micropressure ejection of drugs from multibarreled pipettes

Palmer, Michael R.; Wuerthele, Suzanne M.; Hoffer, Barry J.

doi:10.1016/0028-3908(80)90001-5

Cited by 139 publications

(16 citation statements)

References 15 publications

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“…We assume that the concentration of 5-HT released by pressure pulses is linearly related to the open time of the electrovalve, as demonstrated by Palmer, Wuerthele & Hoffer (1980). Dose-response curves were plotted by calculating the peak amplitude of the responses to pressure pulses of different duration.…”

Section: -Ht Sensitivity Of P Cells In Culturementioning

confidence: 99%

Distribution of receptors for acetylcholine and 5‐hydroxytryptamine on identified leech neurones growing in culture.

Pellegrino¹,

Simonneau²

1984

The Journal of Physiology

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SUMMARY1. The spatial distribution of receptors on identified leech neurones removed from the c.N.s. and grown in culture has been studied by applying acetylcholine (ACh) and 5-hydroxytryptamine (5-HT) ionophoretically and by pressure. Two cells were selected: a neurone called anterior Pagoda (Ap), that shows responses to ACh, and the pressure sensory neurone (P cell), upon which 5-HT synapses form in culture.2. ACh receptors of Ap neurones in culture had properties similar to those of their counterparts in situ. Thus, ACh responses of Ap cells were mediated by Cl-and were blocked by curare and a-bungarotoxin. The cell bodies of these neurones in culture had low (10 mV/nC) and uniform sensitivity to ACh over the surface of the soma.3. When a sprout grew out from the Ap cell, a region of increased sensitivity appeared at its base, with a gradient of sensitivity decreasing toward the tip of the neurite. Characteristically, the base was 3-5 times more sensitive to ACh than the soma or the growth cone. Cells with multipolar processes developed a similar pattern of sensitivity for each sprout.4. P sensory neurones in culture showed similar distributions of sensitivity to 5-HT and ACh.5. Experiments made with voltage clamp suggested that the non-uniform responses to transmitter represent true differences in sensitivity.6. Together these findings suggest that the receptors for ACh and 5-HT have a greater density at the base of each neurite compared to that of the soma and the tip.

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Section: -Ht Sensitivity Of P Cells In Culturementioning

confidence: 99%

Distribution of receptors for acetylcholine and 5‐hydroxytryptamine on identified leech neurones growing in culture.

Pellegrino¹,

Simonneau²

1984

The Journal of Physiology

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“…1 (a and b). After recording their responses, TTX was 'puffed' (20.7 kPa, 1 to 3 s) over the surface of the respective ceils using micro-pressure-ejection techniques (McCaman et al, 1977;Palmer et al, 1980). The toxin (10 -5 g/ml) was applied from a second micropipette (tip diameter 3 ~tm) positioned approx.…”

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confidence: 99%

Loss of Functional Voltage-gated Sodium Channels in Persistent Mumps Virus-infected PC12 Cells

Stauffer

Ziegler²

1989

Journal of General Virology

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SUMMARYRat pheochromocytoma (PC12) cells, persistently infected with mumps virus (MV), failed to generate full-sized stimulus-evoked action potentials (SEAPs) when examined by intracellular electrophysiological recording techniques. Application of tetrodotoxin (TTX) had little or no effect on MV-reduced SEAPs, indicating that the number of functional voltage-gated Na ÷ channels was decreased or their operation was blocked by the virus. In contrast, MV-infected cells generated normal Ca 2+ spikes when bathed in a solution containing TTX, tetraethylammonium ions and a high concentration (20 mM) of Ca 2÷. In addition, when infected cells bathed in TTX were superfused with Co 2÷ the SEAP profile reverted to that typical of PC12 cells with functional voltagegated K ÷ channels only. These observations indicate that MV affects voltage-gated Na + channels, but spares voltage-gated Ca 2+ and K + channels of persistently infected cells.

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“…The data was digitized and quantified by computer analysis to indicate the percent depression or excitation of neuronal activity caused by drug application. Reports from our laboratory have evaluated the ability of this analytic approach to quantitate responses of neurons to microadministration of drugs (21,23). Using these techniques, drug responses can be evaluated independently of changes in background discharge, and apparent antagonism due to changes in release of drug from the pipette can be avoided (23).…”

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confidence: 99%

“…Extracellular action potentials were recorded from single cerebellar Purkinje neurons in lobules VI and VII of the cerebellar vermis through a 5 M NaCl-filled barrel of 3-to 4-barrel micropipettes that were constructed as described (21). This neuronal activity was filtered, monitored on an oscilloscope, and then converted to constant voltage pulses by using a window discriminator.…”

mentioning

confidence: 99%

“…Cerebellar Purkinje neurons were identified by their characteristic discharge pattern of simple and complex spikes. Drugs were applied from one to three barrels of the micropipette by micropressure ejection as described (21). Pressure applications were regulated by a pneumatic valve (1-35 psi; 1 psi = 6.89 kPa), and the timing of drug pulses was controlled by a crystal clock circuit.…”

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confidence: 99%

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Antagonism of phencyclidine action by metaphit in rat cerebellar Purkinje neurons: an electrophysiological study.

Wang¹,

Palmer²,

Freedman³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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Metaphit (1-[1-(3-isothiocyanatophenyl)-cyclohexylipiperidine), a derivative of the psychotomimetic drug phencyclidine (PCP), is postulated to bind irreversibly to PCP receptors. We examined here the electrophysiological interactions ofmetaphit with PCP in rat cerebellar cortex, since a specific effect of PCP on cerebellar neuronal circuitry has been shown. Metaphit, applied locally to Purkinje neurons by micropressure ejection through multibarreled micropipettes, has a reversible depressant action lasting for 5-20 min. Following this, PCP-induced inhibition is blocked with no recovery despite repeated applications ofPCP for over an hour. This blockade was not seen unless the dose of metaphit was sufficient to transiently depress Purkinje neuron discharge. Metaphit does not antagonize inhibitory effects of locally applied norepinephrine or r-aminobutyric acid. This electrophysiological data suggests that metaphit is an irreversible antagonist of PCP in the cerebellum.The violently aggressive behavior and long-lasting psychosis induced by PCP [1-(1-phenylcyclohexyl)piperidine] abuse has caused societal concern in many areas of the United States. The psychosis induced by PCP is similar to that displayed in schizophrenia, and it has been noted that it might serve as a useful drug model for schizophrenia (1). No specific treatment for PCP psychosis is available (2). For these reasons and many others, the mode of action of PCP in the brain has been investigated by many workers (3).Extensive evidence has been obtained for the presence of specific receptors in the brain for PCP and similar compounds. Binding sites for which compounds similar to PCP have high affinity have been noted to be most prevalent in the striatum, cortex, and hippocampal regions of the brain (4-8).There is a high statistical correlation between the binding affinity of these compounds in vitro and their in vivo activity. The stereospecificity of the interaction of compounds similar to PCP with the PCP receptors in vitro and in vivo has also been noted (9)(10)(11). Further, an endogenous ligand for the PCP receptor has been reported (12). Evidence has been obtained that multiple receptors may exist for compounds similar to PCP (4,13,14). Biochemical studies with a new site-directed acylating agent for the PCP receptors have provided further evidence for the existence of multiple receptors for compounds similar to PCP. This affinity ligand, metaphit (1-[1-(3-isothiocyanatophenyl)cyclohexyl]piperidine), irreversibly inactivated only about 50% of the receptors in the striatum and hippocampus, the two brain areas that were investigated (15). The effect of metaphit on the binding of PCP in striatum has been correlated with a diminished behavioral efficacy of PCP (16).Our previous findings strongly suggested that stereospecific PCP-induced depressions of cerebellar Purkinje neurons are mediated by catecholamine pathways (17). The stereospecific effect of the PCP derivative 1-(1-phenylcyclohexyl)-3-methyl-piperidine on cerebellar Purkinje neurons ...

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Physical and physiological characteristics of micropressure ejection of drugs from multibarreled pipettes

Cited by 139 publications

References 15 publications

Distribution of receptors for acetylcholine and 5‐hydroxytryptamine on identified leech neurones growing in culture.

Distribution of receptors for acetylcholine and 5‐hydroxytryptamine on identified leech neurones growing in culture.

Loss of Functional Voltage-gated Sodium Channels in Persistent Mumps Virus-infected PC12 Cells

Antagonism of phencyclidine action by metaphit in rat cerebellar Purkinje neurons: an electrophysiological study.

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