Opposing Inward and Outward Conductances Regulate Rebound Discharges in Olfactory Mitral Cells

2007 ◽  
Vol 97 (3) ◽  
pp. 1959-1968 ◽  
Author(s):  
Ramani Balu ◽  
Ben W. Strowbridge
Keyword(s):  
Olfactory Bulb ◽  
Outward Current ◽  
Membrane Properties ◽  
Transient Outward Current ◽  
Na Channel ◽  
Mitral Cells ◽  
Na Channels ◽  
Spike Generation ◽  
Intrinsic Membrane Properties

The olfactory bulb, a second-order sensory brain region, relays afferent input from olfactory receptor neurons to piriform cortex and other higher brain centers. Although large inhibitory postsynaptic potentials (IPSPs) are evident in in vivo intracellular recordings from mitral cells, the functional significance of these synaptic responses has not been defined. In many brain regions, IPSPs can function to either inhibit spiking by transiently suppressing activity or can evoke spiking directly by triggering rebound discharges. We used whole cell patch-clamp recordings from mitral cells in olfactory bulb slices to investigate the mechanisms by which IPSPs regulate mitral cell spike discharges. Mitral cells have unusual intrinsic membrane properties that support rebound spike generation in response to small-amplitude (3–5 mV) but not large-amplitude hyperpolarizing current injections or IPSPs. Rebound spiking occurring in mitral cells was dependent on recovery of subthreshold Na currents, and could be blocked by tetrodotoxin (TTX, 1 μM) or the subthreshold Na channel blocker riluzole (10 μM). Surprisingly, larger-amplitude hyperpolarizing stimuli impeded spike generation by recruiting a transient outward IA-like current that was sensitive to high concentrations of 4-aminopyridine and Ba. The interplay of voltage-gated subthreshold Na channels and transient outward current produces a narrow range of IPSP amplitudes that generates rebound spikes. We also found that subthreshold Na channels boost subthreshold excitatory stimuli to produce membrane voltages where granule-cell-mediated IPSPs can produce rebound spikes. These results demonstrate how the intrinsic membrane properties of mitral cells enable inhibitory inputs to bidirectionally control spike output from the olfactory bulb.

Dendritic arbor of locus coeruleus neurons contributes to opioid inhibition

1996 ◽  
Vol 75 (5) ◽  
pp. 2029-2035 ◽  
Author(s):  
R. A. Travagli ◽  
M. Wessendorf ◽  
J. T. Williams
Keyword(s):  
Locus Coeruleus ◽  
Horizontal Plane ◽  
Reversal Potential ◽  
Outward Current ◽  
Membrane Properties ◽  
Equilibrium Potential ◽  
Intrinsic Membrane Properties ◽  
In Cells

1. The nucleus locus coeruleus (LC) is made up of noradrenergic cells all of which are hyperpolarized by opioids. Recent work has shown that the reversal potential of the opioid-induced current is more negative than the potassium equilibrium potential. The aim of the present study was to determine whether the extent of the dendritic field could contribute to the very negative opioid reversal potential. 2. Individual LC cells were labeled in the brain slice preparation. The number of dendrites found on cells in slices sectioned in the horizontal plane was greater than cells in coronal slices. However, the dimensions of the cell body slices from each plane were not significantly different. 3. The resting conductance of neurons from slices cut in the horizontal plane was significantly larger than in cells from coronal plane. 4. The amplitude of the outward current induced by [Met5]-enkephalin (ME) was larger in cells from horizontal slices and the reversal potential was more negative than that of cells in coronal slices. 5. The results show that the plane of section influences the membrane properties and opioid actions of LC neurons in vitro and suggest that these differences correlate with the numbers of dendrites. The results suggest that in vivo, in addition to intrinsic membrane properties and synaptic inputs, the structural makeup of the nucleus is an important factor in determining the activity.

scholarly journals Endurance exercise training normalizes repolarization and calcium-handling abnormalities, preventing ventricular fibrillation in a model of sudden cardiac death

2012 ◽  
Vol 113 (11) ◽  
pp. 1772-1783 ◽  
Author(s):  
Ingrid M. Bonilla ◽  
Andriy E. Belevych ◽  
Arun Sridhar ◽  
Yoshinori Nishijima ◽  
Hsiang-Ting Ho ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Exercise Training ◽  
Endurance Exercise ◽  
Cardiac Death ◽  
Outward Current ◽  
Calcium Handling ◽  
Transient Outward Current ◽  
Cellular Electrophysiology ◽  
Endurance Exercise Training

The risk of sudden cardiac death is increased following myocardial infarction. Exercise training reduces arrhythmia susceptibility, but the mechanism is unknown. We used a canine model of sudden cardiac death (healed infarction, with ventricular tachyarrhythmias induced by an exercise plus ischemia test, VF+); we previously reported that endurance exercise training was antiarrhythmic in this model (Billman GE. Am J Physiol Heart Circ Physiol 297: H1171–H1193, 2009). A total of 41 VF+ animals were studied, after random assignment to 10 wk of endurance exercise training (EET; n = 21) or a matched sedentary period ( n = 20). Following (>1 wk) the final attempted arrhythmia induction, isolated myocytes were used to test the hypotheses that the endurance exercise-induced antiarrhythmic effects resulted from normalization of cellular electrophysiology and/or normalization of calcium handling. EET prevented VF and shortened in vivo repolarization ( P < 0.05). EET normalized action potential duration and variability compared with the sedentary group. EET resulted in a further decrement in transient outward current compared with the sedentary VF+ group ( P < 0.05). Sedentary VF+ dogs had a significant reduction in repolarizing K+ current, which was restored by exercise training ( P < 0.05). Compared with controls, myocytes from the sedentary VF+ group displayed calcium alternans, increased calcium spark frequency, and increased phosphorylation of S2814 on ryanodine receptor 2. These abnormalities in intracellular calcium handling were attenuated by exercise training ( P < 0.05). Exercise training prevented ischemically induced VF, in association with a combination of beneficial effects on cellular electrophysiology and calcium handling.

Effects of norepinephrine upon superficial layer neurons in the superior colliculus of the hamster: In vitro studies

1999 ◽  
Vol 16 (3) ◽  
pp. 557-570 ◽  
Author(s):  
HONGJING TAN ◽  
RICHARD D. MOONEY ◽  
ROBERT W. RHOADES
Keyword(s):  
Superior Colliculus ◽  
Optic Tract ◽  
Reversal Potential ◽  
Outward Current ◽  
Input Resistance ◽  
Superficial Layer ◽  
Membrane Properties ◽  
Induced Response

Intracellular recording techniques were used to evaluate the effects of norepinephrine (NE) on the membrane properties of superficial layer (stratum griseum superficiale and stratum opticum) superior colliculus (SC) cells. Of the 207 cells tested, 44.4% (N = 92) were hyperpolarized by ≥3 mV and 8.7% (N = 18) were depolarized by ≥3 mV by application of NE. Hyperpolarization induced by NE was dose dependent (EC50 = 8.1 μM) and was associated with decreased input resistance and outward current which had a reversal potential of −94.0 mV. Depolarization was associated with a very slight rise in input resistance and had a reversal potential of −93.1 mV for the single cell tested. Pharmacologic experiments demonstrated that isoproterenol, dobutamine, and p-aminoclonidine all hyperpolarized SC cells. These results are consistent with the conclusion that NE-induced hyperpolarization of SC cells is mediated by both α2 and β1 adrenoceptors. The α1 adrenoceptor agonists, methoxamine and phenylephrine, depolarized 35% (6 of 17) of the SC cells tested by ≥3 mV. Most of the SC cells tested exhibited responses indicative of expression of more than one adrenoceptor. Application of p-aminoclonidine or dobutamine inhibited transsynaptic responses in SC cells evoked by electrical stimulation of optic tract axons. Inhibition of evoked responses by these agents was usually, but not invariably, associated with a hyperpolarization of the cell membrane and a reduction in depolarizing potentials evoked by application of glutamate. The present in vitro results are consistent with those of the companion in vivo study which suggested that NE-induced response suppression in superficial layer SC neurons was primarily postsynaptic and chiefly mediated by both α2 and β1 adrenoceptors.

scholarly journals Cellular and Synaptic Mechanisms That Differentiate Mitral Cells and Superficial Tufted Cells Into Parallel Output Channels in the Olfactory Bulb

2020 ◽  
Vol 14 ◽  
Author(s):  
Shelly Jones ◽  
Joel Zylberberg ◽  
Nathan Schoppa
Keyword(s):  
Olfactory Bulb ◽  
Plexiform Layer ◽  
Input Resistance ◽  
Cell Types ◽  
Mitral Cells ◽  
Whole Cell ◽  
Wide Range ◽  
Tufted Cells ◽  
Parallel Output

A common feature of the primary processing structures of sensory systems is the presence of parallel output “channels” that convey different information about a stimulus. In the mammalian olfactory bulb, this is reflected in the mitral cells (MCs) and tufted cells (TCs) that have differing sensitivities to odors, with TCs being more sensitive than MCs. In this study, we examined potential mechanisms underlying the different responses of MCs vs. TCs. For TCs, we focused on superficial TCs (sTCs), which are a population of output TCs that reside in the superficial-most portion of the external plexiform layer, along with external tufted cells (eTCs), which are glutamatergic interneurons in the glomerular layer. Using whole-cell patch-clamp recordings in mouse bulb slices, we first measured excitatory currents in MCs, sTCs, and eTCs following olfactory sensory neuron (OSN) stimulation, separating the responses into a fast, monosynaptic component reflecting direct inputs from OSNs and a prolonged component partially reflecting eTC-mediated feedforward excitation. Responses were measured to a wide range of OSN stimulation intensities, simulating the different levels of OSN activity that would be expected to be produced by varying odor concentrations in vivo. Over a range of stimulation intensities, we found that the monosynaptic current varied significantly between the cell types, in the order of eTC &gt; sTC &gt; MC. The prolonged component was smaller in sTCs vs. both MCs and eTCs. sTCs also had much higher whole-cell input resistances than MCs, reflecting their smaller size and greater membrane resistivity. To evaluate how these different electrophysiological aspects contributed to spiking of the output MCs and sTCs, we used computational modeling. By exchanging the different cell properties in our modeled MCs and sTCs, we could evaluate each property's contribution to spiking differences between these cell types. This analysis suggested that the higher sensitivity of spiking in sTCs vs. MCs reflected both their larger monosynaptic OSN signal as well as their higher input resistance, while their smaller prolonged currents had a modest opposing effect. Taken together, our results indicate that both synaptic and intrinsic cellular features contribute to the production of parallel output channels in the olfactory bulb.

Regulation of amiloride-sensitive Na+ channels by endothelin-1 in distal nephron cells

1996 ◽  
Vol 271 (2) ◽  
pp. F451-F460 ◽  
Author(s):  
M. S. Gallego ◽  
B. N. Ling
Keyword(s):  
Na Channel ◽  
Na Channels ◽  
Channel Activity ◽  
Distal Nephron ◽  
Endothelin 1 ◽  
Channel Inhibition ◽  
Current Voltage ◽  
Mean Time ◽  
Current Voltage Relationship

We used patch-clamp methods to investigate the effects of basolateral endothelin-1 (ET-1) on the amiloride-sensitive Na+ channel in A6 distal nephron cells. One hundred picomolar ET-1 decreased channel activity via an increase in mean time closed (P < 0.01, n = 10). Channel inhibition by pM ET-1 was mimicked by an ET-B receptor agonist (P < 0.05, n = 7) and was prevented by ET-B antagonists (P = 0.14, n = 10) but not by an ET-A antagonist (P < 0.05, n = 4). With the inhibitory ET-B receptor blocked, higher doses of ET-1 (10 nM) actually increased channel activity through an increase in mean time open (P < 0.001, n = 12). The current-voltage relationship and the number of channels were not changed by basolateral ET-1 exposure. We conclude that 1) basolateral ET-1 regulates amiloride-sensitive Na+ channels; 2) binding of picomolar ET-1 to ET-B receptors inhibits, whereas the binding of nanomolar ET-1 to a different ET receptor (likely ET-A) stimulates, channel activity; and 3) these dose-dependent, distal nephron responses provide a potential mechanism for the in vivo natriuresis and antinatriuresis observed in response to "subpressor" and "pressor" concentrations of ET-1, respectively.

Role of chloride currents in repolarizing rabbit atrial myocytes

1995 ◽  
Vol 268 (5) ◽  
pp. H1992-H2002 ◽  
Author(s):  
Z. Wang ◽  
B. Fermini ◽  
J. Feng ◽  
S. Nattel
Keyword(s):  
Action Potential ◽  
Reversal Potential ◽  
Outward Current ◽  
Cell Voltage ◽  
Disulfonic Acid ◽  
Transient Outward Current ◽  
Atrial Myocytes ◽  
Atrial Cells ◽  
K Current

Rabbit atrial cells manifest a prominent transient outward K+ current (Ito1), but this current recovers slowly from inactivation and is unlikely to be important at physiological rates (3-5 Hz). Depolarization of rabbit atrial cells also elicits a transient Ca(2+)-dependent outward Cl- current (Ito2). To compare the relative magnitude of these transient outward currents at various rates, we applied whole cell voltage-clamp techniques to isolated rabbit atrial myocytes. Whereas peak Ito1 exceeded Ito2 at slow rates (0.1 Hz), Ito1 was strongly reduced as rate was increased (by 97 +/- 2%, mean +/- SE, at 4 Hz), while Ito2 was slightly reduced (by 28 +/- 4%, 4 Hz). The reversal potential of transient outward tail currents at 0.07 Hz was -49 +/- 9 mV, while at 2.5 Hz the reversal potential became -18 +/- 7 mV (calculated Cl- reversal potential -18 mV). The addition of the Cl- transport blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS; 150 microM) or the replacement of external Cl- with methanesulfonate inhibited a large part of the transient outward current elicited by depolarization at 4 Hz. DIDS and Cl- replacement increased action potential duration in both single rabbit atrial cells and multicellular rabbit atrial preparations. We conclude that the Ca(2+)-dependent Cl- current is substantially larger than the transient K+ current at physiological rates in the rabbit and is likely to play a more important role in action potential repolarization than the latter current in this tissue in vivo.

Direct Excitation of Mitral Cells Via Activation of α1-Noradrenergic Receptors in Rat Olfactory Bulb Slices

2001 ◽  
Vol 86 (5) ◽  
pp. 2173-2182 ◽  
Author(s):  
Abdallah Hayar ◽  
Phillip M. Heyward ◽  
Thomas Heinbockel ◽  
Michael T. Shipley ◽  
Matthew Ennis
Keyword(s):  
Olfactory Bulb ◽  
Locus Coeruleus ◽  
Equilibrium Potential ◽  
Channel Blockers ◽  
Mitral Cells ◽  
Patch Clamp Recording ◽  
Whole Cell ◽  
Inward Current

The main olfactory bulb receives a significant modulatory noradrenergic input from the locus coeruleus. Previous in vivo and in vitro studies showed that norepinephrine (NE) inputs increase the sensitivity of mitral cells to weak olfactory inputs. The cellular basis for this action of NE is not understood. The goal of this study was to investigate the effect of NE and noradrenergic agonists on the excitability of mitral cells, the main output cells of the olfactory bulb, using whole cell patch-clamp recording in vitro. The noradrenergic agonists, phenylephrine (PE, 10 μM), isoproterenol (Isop, 10 μM), and clonidine (3 μM), were used to test for the functional presence of α1-, β-, and α2-receptors, respectively, on mitral cells. None of these agonists affected olfactory nerve (ON)–evoked field potentials recorded in the glomerular layer, or ON-evoked postsynaptic currents recorded in mitral cells. In whole cell voltage-clamp recordings, NE (30 μM) induced an inward current (54 ± 7 pA, n= 16) with an EC50 of 4.7 μM. Both PE and Isop also produced inward currents (22 ± 4 pA, n = 19, and 29 ± 9 pA, n = 8, respectively), while clonidine produced no effect ( n = 6). In the presence of TTX (1 μM), and blockers of excitatory and inhibitory fast synaptic transmission [gabazine 5 μM, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) 10 μM, and (±)-2-amino-5-phosphonopentanoic acid (APV) 50 μM], the inward current induced by PE persisted (EC50 = 9 μM), whereas that of Isop was absent. The effect of PE was also observed in the presence of the Ca2+ channel blockers, cadmium (100 μM) and nickel (100 μM). The inward current caused by PE was blocked when the interior of the cell was perfused with the nonhydrolyzable GDP analogue, GDPβS, indicating that the α1 effect is mediated by G-protein coupling. The current-voltage relationship in the absence and presence of PE indicated that the current induced by PE decreased near the equilibrium potential for potassium ions. In current-clamp recordings from bistable mitral cells, PE shifted the membrane potential from the downstate (−52 mV) toward the upstate (−40 mV), and significantly increased spike generation in response to perithreshold ON input. These findings indicate that NE excites mitral cells directly via α1 receptors, an effect that may underlie, at least in part, increased mitral cell responses to weak ON input during locus coeruleus activation in vivo.

Phasic Stimuli Evoke Precisely Timed Spikes in Intermittently Discharging Mitral Cells

2004 ◽  
Vol 92 (2) ◽  
pp. 743-753 ◽  
Author(s):  
Ramani Balu ◽  
Phillip Larimer ◽  
Ben W. Strowbridge
Keyword(s):  
Olfactory Bulb ◽  
Action Potentials ◽  
Sensory Stimulation ◽  
Spike Timing ◽  
Mitral Cells ◽  
Potential Oscillations ◽  
Sensory Stimuli ◽  
Subthreshold Oscillations ◽  
Simple Step

Mitral cells, the principal cells of the olfactory bulb, respond to sensory stimulation with precisely timed patterns of action potentials. By contrast, the same neurons generate intermittent spike clusters with variable timing in response to simple step depolarizations. We made whole cell recordings from mitral cells in rat olfactory bulb slices to examine the mechanisms by which normal sensory stimuli could generate precisely timed spike clusters. We found that individual mitral cells fired clusters of action potentials at 20-40 Hz, interspersed with periods of subthreshold membrane potential oscillations in response to depolarizing current steps. TTX (1 μM) blocked a sustained depolarizing current and fast subthreshold oscillations in mitral cells. Phasic stimuli that mimic trains of slow excitatory postsynaptic potentials (EPSPs) that occur during sniffing evoked precisely timed spike clusters in repeated trials. The amplitude of the first simulated EPSP in a train gated the generation of spikes on subsequent EPSPs. 4-aminopyridine (4-AP)–sensitive K+ channels are critical to the generation of spike clusters and reproducible spike timing in response to phasic stimuli. Based on these results, we propose that spike clustering is a process that depends on the interaction between a 4-AP–sensitive K+ current and a subthreshold TTX-sensitive Na+ current; interactions between these currents may allow mitral cells to respond selectively to stimuli in the theta frequency range. These intrinsic properties of mitral cells may be important for precisely timing spikes evoked by phasic stimuli that occur in response to odor presentation in vivo.

scholarly journals Regulation of Na channels of the rat cortical collecting tubule by aldosterone.

1993 ◽  
Vol 102 (1) ◽  
pp. 25-42 ◽  
Author(s):  
J Pácha ◽  
G Frindt ◽  
L Antonian ◽  
R B Silver ◽  
L G Palmer
Keyword(s):  
Membrane Surface ◽  
Plasma Aldosterone ◽  
Na Channel ◽  
Na Channels ◽  
Channel Activity ◽  
Open Probability ◽  
Collecting Tubule ◽  
Salt Depletion ◽  
Cortical Collecting Tubule

The activity of apical membrane Na channels in the rat cortical collecting tubule was studied during manipulation of the animals' mineralocorticoid status in vivo using a low-Na diet or the diuretic furosemide. Tubules were isolated and split open to expose the luminal membrane surface. Induction of Na channel activity was studied in cell-attached patches of the split tubules. No activity was observed with control animals on a normal diet. Channel activity could be induced by putting the animals on the low-Na diet for at least 48 h. The mean number of open channels per patch (NPo) was maximal after 1 wk on low Na. Channels were also induced within 3 h after injection of furosemide (20 mg/kg body wt per d). NPo was maximal 48 h after the first injection. In both cases, increases in NPo were primarily due to increases in the number of channels per patch (N) at a constant open probability (Po). With salt depletion or furosemide injection NPo is a saturable function of aldosterone concentration with half-maximal activity at approximately 8 nM. When animals were salt repleted after 1-2 wk of salt depletion, both plasma aldosterone and NPo fell markedly within 6 h. NPo continued to decrease over the next 14 h, while plasma aldosterone rebounded partially. Channel activity may be dissociated from aldosterone concentrations under conditions of salt repletion.

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