Biomedical subjects

S Madamba

Publications and source records attributed to S Madamba.

5 recordsLinked to original sources

PubMed1992

Concentrations of carbachol stimulating phosphoinositide hydrolysis cause a sustained decrease in membrane potential and firing rate: role of inositol and inositol polyphosphate second messengers.

We have investigated the relationship between muscarinic agonist-stimulated phosphoinositide (PI) hydrolysis and electrophysiological responses in rat hippocampal slice preparations. In a previous extracellular study, we found that muscarinic agonists at concentrations that stimulate PI hydrolysis result in a biphasic firing response; an initial increase in firing followed by loss of firing at higher concentrations. To test the hypothesis that variability in obtaining consistent loss of firing is related to depletion of intracellular inositol, we investigated the effects of adding exogenous inositol to the buffer. We now report that concentrations of inositol similar to those in cerebral spinal fluid (30-100 microM) augment carbamylcholine (carbachol, CCh) mediated loss of firing and [3H]inositol-1,3,4,5-tetrakisphosphate ([3H]Ins(1,3,4,5)P4) formation. Inhibition of firing produced by 30 microM CCh in the presence of inositol was associated with a sustained depolarization of 20-25 mV, an increased slope resistance in the depolarized range (-60 to -40 mV), and a parallel shift in the hyperpolarized (-100 to -70 mV) range of the voltage-current curve and increased frequency of spontaneous IPSPs. Under voltage-clamp, measurements of the M-current (IM) showed sustained inactivation by CCh with reversal after washout of CCh. Manual depolarization of cells by current injection to the same level of depolarization as attained with CCh did not usually lead to the same loss of firing. These findings suggest that IM, and possibly other voltage-independent currents or ion pumps, may cause loss of firing only in part through a depolarization blockade of firing and not through desensitization. Furthermore, CCh treatment without inositol did not depolarize neurons as much as CCh with inositol, and usually did not cause a delayed loss of firing. Brain slice preparations may thus require physiological concentrations of inositol to show consistent or maximum phosphoinositide-mediated electrophysiological responses.

Action Potentials↗

PubMed1992

Interleukin-1 beta increases synaptic inhibition in rat hippocampal pyramidal neurons in vitro.

Interleukin-1 (IL-1), a cytokine with a broad spectrum of biological activity, modulates electrical properties of central neurons in the brain. The effects of IL-1 beta (143 pM) on conductances opened by synaptic stimulation of the Schaffer collaterals were studied by intracellular recording of hippocampal pyramidal cells of the CA1 region. IL-1 beta enhanced and prolonged synaptic inhibition by about 2 to 3-fold. Heat-inactivated IL-1 beta had no effect. This finding implies that IL-1 beta changes interneuronal communication in the hippocampus with a possible impact on neuronal plasticity.

Animals↗

PubMed1992

Opioid peptides reduce synaptic transmission in the nucleus accumbens.

Behavioral studies implicate the nucleus accumbens (NAcc) as a brain area pivotal for the rewarding effects of opiates like heroine and morphine. Therefore, we studied the effect of a variety of opioids on membrane properties and responses to synaptic stimulation in a slice preparation of the NAcc using intracellular recording. Superfusion of opioid peptides did not affect the membrane potential or input resistance of NAcc neurons, but significantly reduced both depolarizing and hyperpolarizing synaptic potentials. Naloxone superfusion significantly reversed the depressant effects of the mu and delta receptor agonists (but not those of the kappa agonist) on synaptic transmission, suggesting involvement of opiate receptors. These results imply that the predominant effect of opiates in NAcc is a reduction of synaptic transmission.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1990

Arachidonic acid metabolites as mediators of somatostatin-induced increase of neuronal M-current.

The M-current (IM) is a time- and voltage-dependent K+ current that persists at slightly depolarized membrane potentials. IM is reduced by muscarinic cholinergic agonists and certain peptides, and is thought to be responsible in part for the slow and late slow excitatory postsynaptic potentials in sympathetic neurons. Recently, we reported that IM in hippocampal neurons was also augmented by somatostatin-14 and -28 suggesting that two different receptors reciprocally regulate one neuronal channel type. Muscarinic effects on IM may be mediated by various components of the phosphatidylinositol phosphate pathway. We now report the involvement of a different second messenger pathway, that generated by phospholipase A2, in the somatostatin-induced augmentation of IM in hippocampal cells. This pathway generates arachidonic acid from which leukotrienes can be produced by lipoxygenases. We find that the IM-augmenting effects of somatostatin are abolished by two substances that can inhibit phospholipase A2, quinacrine and 4-bromophenacyl bromide, and that both arachidonic acid and leukotriene C4 mimic the effects of somatostatin-14 on hippocampal pyramidal neurons in vitro. Arachidonic and somatostatin effects are blocked by a lipoxygenase inhibitor, implicating an arachidonic acid metabolite, perhaps a leukotriene, in the somatostatin effect.

Acetophenones↗

PubMed1988

Somatostatin depresses excitability in neurons of the solitary tract complex through hyperpolarization and augmentation of IM, a non-inactivating voltage-dependent outward current blocked by muscarinic agonists.

The synaptic function of somatostatin-containing fibers in the nervous system is controversial. Therefore, we used a slice preparation of the rat brain stem to test the electrophysiological effects of prosomatostatin-derived peptides on neurons of the solitary tract complex, which contains an abundance of somatostatin-containing fibers and cell bodies. Superfusion of both somatostatin-14 and somatostatin-28 (the precursor for somatostatin-14), but not somatostatin-28-(1-12) or -(1-10), predominantly inhibited spontaneous spike and subthreshold (probably synaptic) activity. In intracellular recordings, somatostatin-14 and -28 hyperpolarized most neurons in association with a slight (10-35%) but reproducible decrease in input resistance. These hyperpolarizing responses were augmented in depolarized cells and persisted in cells in which spontaneous inhibitory postsynaptic potentials became depolarizing after Cl- injection. These data suggest that somatostatin receptors regulate a K+ conductance. In voltage-clamp studies, somatostatin-28 and -14 induced a steady outward current and augmented the voltage-dependent, nonactivating outward K+ conductance (IM) shown to be blocked by activation of muscarinic cholinergic receptors. These results suggest (i) that somatostatin-containing elements in the solitary tract complex play an inhibitory role through the activation of postsynaptic permeability to potassium ions and (ii) that the same ion channel type may be coregulated by two neurotransmitter candidates, somatostatin and acetylcholine, through a reciprocal control mechanism.

Animals↗