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D A Baxter

Publications and source records attributed to D A Baxter.

44 records · Page 3Linked to original sources
PubMed1990

Reduction of voltage-activated K+ currents by forskolin is not mediated via cAMP in pleural sensory neurons of Aplysia.

1. Forskolin is often used to activate adenylate cyclase in studies relating adenosine 3',5'-cyclic monophosphate (cAMP) to the modulation of membrane current. There is growing concern, however, that some actions of forskolin are independent of cAMP. With the use of two-electrode voltage-clamp techniques, we compared the effects of analogues of cAMP to the effects of forskolin on K+ currents in somata of sensory neurons that were isolated from pleural ganglia of Aplysia californica. 2. Analogues of cAMP did not reduce the peak amplitude of either the transient K+ current (IA) or the voltage-dependent K+ current (IK.V). Analogues of cAMP did reduce the previously described cAMP-sensitive S K+ current (IK.S). In contrast, forskolin reduced the peak amplitude of both IA and IK.V. Furthermore, both IA and IK.V were reduced by 1,9-dideoxy-forskolin, a derivative of forskolin that does not activate adenylate cyclase. These results indicate that the effects of forskolin and 1,9-dideoxy-forskolin on IA and IK.V were not mediated via cAMP. 3. Bath application of a modified form of forskolin (7-deacetyl-6-[N-acetylglycyl]-forskolin), which has enhanced water solubility and activates adenylate cyclase, reduced IK.S, but did not alter either IA or IK.V. Thus it appears that certain derivatives of forskolin can be used to activate adenylate cyclase and avoid some of the nonspecific actions on membrane current that are associated with forskolin.

Adenylyl Cyclase Inhibitors↗
PubMed1989

"Enacted" auditory images are ambiguous; "pure" auditory images are not.

Previous research indicates that visual images are inherently unambiguous. The present study extends this argument to auditory imagery. In Experiment 1, subjects were able to reinterpret an imaged ambiguous auditory figure, but covert subvocalization apparently aided this reinterpretation. When subvocalization was blocked, reinterpretations were eliminated. Experiments 2 and 3 generalize this finding to different procedures and stimuli. Experiment 4 explores further the role of subvocalization, by showing that the likelihood of reinterpreting an imaged stimulus is directly proportional to the degree of enactment allowed. We argue that subvocalization or enactment provides an internal stimulus that is subject to reinterpretation. Without enactment, the "pure" auditory image is as unambiguous as a visual image. Thus, in both visual and auditory modalities, images come into being as representations and so are inherently meaningful.

Adult↗
PubMed1989

Serotonergic modulation of two potassium currents in the pleural sensory neurons of Aplysia.

1. The properties of membrane currents that were modulated by serotonin (5-HT) were investigated with two-electrode voltage-clamp techniques in sensory neuron somata isolated from the pleural ganglion of Aplysia californica. The modulatory effects of 5-HT were revealed by computer subtraction of current responses elicited in the presence of 5-HT from current responses elicited prior to the application of 5-HT. The complexities of the resulting 5-HT difference currents (I5-HT) suggested that 5-HT modulated more than one component of membrane current. 2. The 5-HT difference currents appeared to have at least two distinct components. One component was clearly evident at membrane potentials more negative than -10 mV was relatively voltage independent and did not inactivate. A second component was activated at membrane potentials more positive than -10 mV, had complex kinetics, and was highly voltage dependent. In an attempt to identify the membrane currents that were modulated by 5-HT, we compared the pharmacologic sensitivity of I5-HT to that of previously described K+ currents. 3. The two components of I5-HT had different sensitivities to agents that block K+ currents. The relatively voltage-independent component of I5-HT was not blocked by 2 mM 4-aminopyridine (4-AP) and was relatively insensitive to tetraethylammonium (TEA) (estimated Kd of 92 mM). In contrast, the voltage-dependent component of I5-HT was blocked by 4-AP (2 mM) and moderate concentrations of TEA (estimated Kd of 5 mM). 4. The K+ current blockers that were used to examine I5-HT were also used to examine voltage-activated membrane currents. Externally applied TEA blocked the delayed or voltage-dependent K+ current (IK.V) with an estimated dissociation constant (Kd) of 8 mM and a membrane current similar to the Ca2+-activated K+ current (IK.Ca) with an estimated Kd of 0.4 mM. In addition, externally applied 4-AP (2 mM) blocked IK.V. Thus TEA and 4-AP were equipotent in blocking both IK.V and the voltage-dependent component of I5-HT. 5. The suggestion that I5-HT contained multiple components was supported further by examining the modulatory effects of adenosine 3',5'-cyclic monophosphate (cAMP) that mediates some actions of 5-HT on membrane currents in these cells. cAMP difference currents (IcAMP) were similar to the relatively voltage-independent component of I5-HT. The subsequent addition of 5-HT to solutions already containing cAMP resulted in 5-HT difference currents similar to the voltage-dependent component of I5-HT.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Mathematical model of cellular mechanisms contributing to presynaptic facilitation.

Presynaptic facilitation of transmitter release from sensory neurons is an important mechanism contributing to nonassociative and associative learning in Aplysia. In a previous modeling study (28,29), we concluded that enhancement of the postsynaptic potential (PSP) during presynaptic facilitation is mediated by at least two processes; spike broadening, which has been observed experimentally, and a process that we modeled as mobilization of transmitter. In an effort to gain insight into the relative contribution of these two mechanisms of presynaptic facilitation, we have extended our earlier model to include more detailed descriptions of: a) the kinetics of the Ca2+ channel, b) the diffusion of Ca2+ through the cytoplasm, c) the process of transmitter release, and d) the PSP. The present quantitative model provides an accurate description of the input-output relationship for synapses of sensory neurons, and predicts changes in the shape of postsynaptic potentials as a function of mobilization and spike broadening. The results confirm and extend previous experimental studies (33) and indicated that cellular analogs of sensitization (facilitation of nondecremented responses) is mediated primarily by spike broadening; whereas, analogs of dishabituation (facilitation of depressed responses) require mobilization.

Animals↗
PubMed1985

Quantal mechanism of long-term synaptic potentiation.

Intracellular recordings were used to demonstrate the occurrence and to analyze the microphysiology of long-term synaptic potentiation (LTP) in the crayfish opener neuromuscular synapse. Brief stimulation of the single excitor motor axon enhanced the amplitudes of subsequent postsynaptic potentials for several hours. Three methods of quantal analysis were used to evaluate the mechanism responsible for LTP. The results of all three methods supported predictions of the hypothesis that LTP results from a presynaptic mechanism that increases the average of neurotransmitter quanta evoked by nerve impulses in the excitor axon.

Animals↗
PubMed1983

Protease inhibitors implicate metalloendoprotease in synaptic transmission at the mammalian neuromuscular junction.

Metalloendoproteases have been implicated in the calcium-dependent exocytosis of histamine from mast cells and in the calcium-dependent fusion of myoblasts. Because metalloendoproteases have also been identified in nervous tissue, we investigated the possibility that these proteases may be involved in neurotransmitter release at mammalian synapses. End-plate potentials were recorded intracellularly from mouse diaphragm/phrenic nerve preparations in vitro. The amplitude of the endplate potentials were reduced by as much as 90% during bath application of phosphoramidon, a specific inhibitor of metalloendoproteases, and by carbobenzoxy-dipeptide-amide synthetic substrates for metalloendoproteases. Only those synthetic dipeptides in which the amino group of the peptide bond was provided by a bulky hydrophobic amino acid, such as phenylalanine or leucine, which are substrates for metalloendoproteases, reduced synaptic transmission. Synthetic substrates in which proline or glycine provided the amino group of the peptide bond, which are not metalloendoprotease substrates, had little or no effect on the amplitude of end-plate potentials. The ability of synthetic substrates to reduce synaptic transmission was also dependent on the amino acid that provided the carboxyl group of the peptide bond, with glycine being more effective than tyrosine or serine. In addition, synthetic dipeptides with free carboxyl or amino termini, which have a low affinity for metalloendoproteases, also had little effect on synaptic transmission. The inhibition of synaptic transmission by phosphoramidon and the synthetic substrates occurred within 2 to 3 min and was completely reversible. Neither phosphoramidon nor the synthetic substrates altered the dose-response characteristics of the postsynaptic membrane to bath-applied carbachol. These results suggest that synaptic transmission requires the activity of a metalloendoprotease in the presynaptic nerve terminal and that proteolysis may be an important step during neurotransmitter exocytosis.

Animals↗
PubMed1981

Intracellular recordings from crustacean motor axons during presynaptic inhibition.

Action potentials intracellularly recorded from near the nerve terminals of the opener excitor motor axon in crayfish are reduced in amplitude during presynaptic inhibition. The amplitude and sign (hyperpolarizing or depolarizing) of presynaptic inhibitor potentials (PIPs) depends upon the relationship between the resting membrane potential of each excitor axon and its PIP equilibrium potential (which equals the equilibrium potential for gamma-aminobutyric acid).

Action Potentials↗