Ionic basis for serotonin-induced bistable membrane properties in guinea pig trigeminal motoneurons. 1998

C F Hsiao, and C A Del Negro, and P R Trueblood, and S H Chandler
Department of Physiological Science, University of California at Los Angeles, Los Angeles, 90095-1568, USA.

Intracellular recordings and pharmacological manipulations were employed to investigate the ionic basis for serotonin-induced bistable membrane behaviors in guinea pig trigeminal motoneurons (TMNs). In voltage clamp, 10 microM serotonin (5-HT) induced a region of negative slope resistance (NSR) in the steady-state current-voltage (I-V) relationship at potentials less negative than -58 mV, creating the necessary conditions for membrane bistability. The contributions of sustained Na+ and Ca2+ currents to the generation of the NSR were investigated using specific ion channel antagonists and agonists. The NSR was eliminated by the L-type Ca2+ channel antagonist nifedipine (5-10 microM), indicating the contribution of L channels. In nifedipine, inward rectification was present in the I-V relationship in a similar voltage range (greater than -58 mV). This region was subsequently linearized by tetrodotoxin (TTX), indicating the presence of a persistent Na+ current. When the 5-HT-induced NSR was eliminated by perfusion in low Ca2+ solution (0.4 mM), it was restored by the Na+ channel agonist veratridine (10 microM). Commensurate with bistability, in current clamp during bath application of 5-HT, plateau potentials were elicited by transient depolarizing or hyperpolarizing stimuli. Plateau potentials evoked by depolarization were observed under control and TTX conditions, but were blocked by nifedipine, suggesting the participation of an L-type Ca2+ current. Plateau potentials initiated after release from hyperpolarization (anode break) were blocked by 300 microM Ni2+, suggesting the responses relied on deinactivation of a T-type Ca2+ current. Conditional bursting was also observed in 5-HT. Nifedipine or low Ca2+ solutions blocked bursting, and the L-channel agonist Bay K 8644 (10 microM) extended the duration of individual bursts, demonstrating the role of L-type Ca2+ currents. Interestingly, when bursting was blocked by nifedipine or low Ca2+, it could be restored by veratridine application via enhancement of the persistent Na+ current. We conclude that bistable membrane behaviors in TMNs are mediated by L-type Ca2+ and persistent Na+ currents. 5-HT is associated with enhancement of TMN activity during oral-motor activity; the induction of bistable membrane properties by 5-HT represents a cellular mechanism for this enhancement.

UI MeSH Term Description Entries
D007473 Ion Channels Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS. Membrane Channels,Ion Channel,Ionic Channel,Ionic Channels,Membrane Channel,Channel, Ion,Channel, Ionic,Channel, Membrane,Channels, Ion,Channels, Ionic,Channels, Membrane
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D008566 Membranes Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures. Membrane Tissue,Membrane,Membrane Tissues,Tissue, Membrane,Tissues, Membrane
D009046 Motor Neurons Neurons which activate MUSCLE CELLS. Neurons, Motor,Alpha Motorneurons,Motoneurons,Motor Neurons, Alpha,Neurons, Alpha Motor,Alpha Motor Neuron,Alpha Motor Neurons,Alpha Motorneuron,Motoneuron,Motor Neuron,Motor Neuron, Alpha,Motorneuron, Alpha,Motorneurons, Alpha,Neuron, Alpha Motor,Neuron, Motor
D009543 Nifedipine A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. Adalat,BAY-a-1040,Bay-1040,Cordipin,Cordipine,Corinfar,Fenigidin,Korinfar,Nifangin,Nifedipine Monohydrochloride,Nifedipine-GTIS,Procardia,Procardia XL,Vascard,BAY a 1040,BAYa1040,Bay 1040,Bay1040,Monohydrochloride, Nifedipine,Nifedipine GTIS
D002120 Calcium Channel Agonists Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture. Calcium Channel Activators,Calcium Channel Agonists, Exogenous,Calcium Channel Agonist,Exogenous Calcium Channel Agonists,Activators, Calcium Channel,Agonist, Calcium Channel,Agonists, Calcium Channel,Channel Activators, Calcium,Channel Agonist, Calcium,Channel Agonists, Calcium
D002121 Calcium Channel Blockers A class of drugs that act by selective inhibition of calcium influx through cellular membranes. Calcium Antagonists, Exogenous,Calcium Blockaders, Exogenous,Calcium Channel Antagonist,Calcium Channel Blocker,Calcium Channel Blocking Drug,Calcium Inhibitors, Exogenous,Channel Blockers, Calcium,Exogenous Calcium Blockader,Exogenous Calcium Inhibitor,Calcium Channel Antagonists,Calcium Channel Blocking Drugs,Exogenous Calcium Antagonists,Exogenous Calcium Blockaders,Exogenous Calcium Inhibitors,Antagonist, Calcium Channel,Antagonists, Calcium Channel,Antagonists, Exogenous Calcium,Blockader, Exogenous Calcium,Blocker, Calcium Channel,Blockers, Calcium Channel,Calcium Blockader, Exogenous,Calcium Inhibitor, Exogenous,Channel Antagonist, Calcium,Channel Blocker, Calcium,Inhibitor, Exogenous Calcium
D002586 Cesium A member of the alkali metals. It has an atomic symbol Cs, atomic number 55, and atomic weight 132.91. Cesium has many industrial applications, including the construction of atomic clocks based on its atomic vibrational frequency. Caesium,Caesium-133,Cesium-133,Caesium 133,Cesium 133
D004594 Electrophysiology The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea

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