scholarly journals Maternal Diabetes Increases Small Conductance Ca2+‐activated K+ (SK) Currents Which Alters Action Potential Properties and Excitability of Cardiac Motoneurons in the Nucleus Ambiguus

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Min Lin ◽  
Qing‐Hui Chen ◽  
Lihua Li ◽  
Robert D Wurster ◽  
Zixi (Jack) Cheng
Keyword(s):  
Action Potential ◽  
Maternal Diabetes ◽  
Nucleus Ambiguus ◽  
Small Conductance

scholarly journals Maternal Diabetes Increases Small Conductance Ca2+-Activated K+ (SK) Currents That Alter Action Potential Properties and Excitability of Cardiac Motoneurons in the Nucleus Ambiguus

2010 ◽  
Vol 104 (4) ◽  
pp. 2125-2138 ◽  
Author(s):  
Min Lin ◽  
Qing-Hui Chen ◽  
Robert D. Wurster ◽  
Jeff T. Hatcher ◽  
Ye-Qi Liu ◽  
...  
Keyword(s):  
Action Potential ◽  
Firing Rate ◽  
Maternal Diabetes ◽  
Spike Frequency ◽  
Nucleus Ambiguus ◽  
Peak Amplitude ◽  
Sk Channels ◽  
Transient Currents ◽  
Whole Cell ◽  
Small Conductance

Parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus (NA) play a key role in regulating cardiac functions. In this study, we examined the effects of maternal diabetes on excitability, action potential (AP) properties, and small conductance Ca2+-activated K+ (SK) currents of PCMNs. Neonatal mice from diabetic (OVE26 female, NMDM) and normal (FVB female, control) mothers that had been mated with nondiabetic fathers (FVB male) were used. Tracer XRITC was injected into the pericardial sac at P7-9 to retrogradely label PCMNs. Two days later, XRITC-labeled PCMNs were identified in brain stem slices. The responses of spike frequency, AP repolarization (half-width) and afterhyperpolarization (AHP) of PCMNs to current injections were studied using whole cell current clamp. Outward and afterhyperpolarization currents ( IAHP) in response to voltage steps were measured using whole cell voltage clamp. In examining the effects of maternal diabetes on excitability and AP properties, we found that in NMDM spike frequency decreased, the half-width and AHP peak amplitude increased, and the peak amplitude of outward transient currents and IAHP increased compared with those measured in control. In examining the effects of maternal diabetes on SK channels, we found that after blockage of SK channels with a specific SK channel blocker apamin, maternal diabetes significantly increased apamin-sensitive outward transient currents and IAHP, and suppressed AHP amplitude in NMDM more than those in control. Further, apamin application increased the firing rate to current injections and completely abolished the difference of the firing rate between control and NMDM. We suggest that the augmented SK-mediated currents may contribute to the increased AHP amplitude and the attenuated excitability of PCMNs in NMDM.

SK channel blockade prevents hypoxia-induced ventricular arrhythmias through inhibition of Ca2+/voltage uncoupling in hypertrophied hearts

2021 ◽  
Vol 320 (4) ◽  
pp. H1456-H1469
Author(s):  
Masayuki Takahashi ◽  
Hisashi Yokoshiki ◽  
Hirofumi Mitsuyama ◽  
Masaya Watanabe ◽  
Taro Temma ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Ventricular Arrhythmias ◽  
Channel Blockade ◽  
Sk Channel ◽  
Small Conductance

We demonstrated that hypoxia-induced ventricular arrhythmias were mainly initiated by Ca2+-loaded triggered activities in hypertrophied hearts. The blockades of small-conductance Ca2+-activated K+ channels, especially “apamin,” showed anti-arrhythmic effects by alleviation of not only action potential duration shortening but also Ca2+ handling abnormalities, most notably the “Ca2+/voltage uncoupling.”

Electrophysiological properties of neurons within the nucleus ambiguus of adult guinea pigs

1991 ◽  
Vol 66 (3) ◽  
pp. 744-761 ◽  
Author(s):  
S. M. Johnson ◽  
P. A. Getting
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Outward Current ◽  
Nucleus Ambiguus ◽  
Transient Outward Current ◽  
Maximum Magnitude ◽  
Action Potential Firing ◽  
Onset Of Action ◽  
Electrophysiological Properties ◽  
Single Action

1. The purpose of this study was to determine the electrophysiological properties of neurons within the region of the nucleus ambiguus (NA), an area that contains the ventral respiratory group. By the use of an in vitro brain stem slice preparation, intracellular recordings from neurons in this region (to be referred to as NA neurons, n = 235) revealed the following properties: postinhibitory rebound (PIR), delayed excitation (DE), adaptation, and posttetanic hyperpolarization (PTH). NA neurons were separated into three groups on the basis of their expression of PIR and DE: PIR cells (58%), DE cells (31%), and Non cells (10%). Non cells expressed neither PIR nor DE and no cells expressed both PIR and DE. 2. PIR was a transient depolarization that produced a single action potential or a burst of action potentials when the cell was released from hyperpolarization. In the presence of tetrodotoxin (TTX), the maximum magnitude of PIR was 7-12 mV. Under voltage-clamp conditions, hyperpolarizing voltage steps elicited a small inward current during the hyperpolarization and a small inward tail current on release from hyperpolarization. These currents, which mediate PIR, were most likely due to Q-current because they were blocked with extracellular cesium and were insensitive to barium. 3. DE was a delay in the onset of action potential firing when cells were hyperpolarized before application of depolarizing current. When cells were hyperpolarized to -90 mV for greater than or equal to 300 ms, maximum delays ranged from 150 to 450 ms. The transient outward current underlying DE was presumed to be A-current because of the current's activation and inactivation characteristics and its elimination by 4-aminopyridine (4-AP). 4. Adaptation was examined by applying depolarizing current for 2.0 s and measuring the frequency of evoked action potentials. Although there was a large degree of variability in the degree of adaptation, PIR cells tended to express less adaptation than DE and Non cells. Nearly three-fourths of all NA neurons adapted rapidly (i.e., 50% adaptation in less than 200 ms), but PIR cells tended to adapt faster than DE and Non cells. PTH after a train of action potentials was relatively rare and occurred more often in DE cells (43%) and Non cells (33%) than in PIR cells (13%). PTH had a magnitude of up to 18 mV and time constants that reflected the presence of one (1.7 +/- 1.4 s, mean +/- SD) or two components (0.28 +/- 0.13 and 4.1 +/- 2.2 s).(ABSTRACT TRUNCATED AT 400 WORDS)

Afterhyperpolarization Current in Myenteric Neurons of the Guinea Pig Duodenum

2001 ◽  
Vol 85 (5) ◽  
pp. 1941-1951 ◽  
Author(s):  
Fivos Vogalis ◽  
John B. Furness ◽  
Wolf A. A. Kunze
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Dwell Time ◽  
High Probability ◽  
Resting Potential ◽  
Bathing Solution ◽  
Inward Current ◽  
Current Pulses ◽  
Mean Variance ◽  
Small Conductance

Whole cell patch and cell-attached recordings were obtained from neurons in intact ganglia of the myenteric plexus of the guinea pig duodenum. Two classes of neuron were identified electrophysiologically: phasically firing AH neurons that had a pronounced slow afterhyperpolarization (AHP) and tonically firing S neurons that lacked a slow AHP. We investigated the properties of the slow AHP and the underlying current ( I AHP) to address the roles of Ca2+ entry and Ca2+ release in the AHP and the characteristics of the K+channels that are activated. AH neurons had a resting potential of −54 mV and the AHP, which followed a volley of three suprathreshold depolarizing current pulses delivered at 50 Hz through the pipette, averaged 11 mV at its peak, which occurred 0.5–1 s following the stimulus. The duration of these AHPs averaged 7 s. Under voltage-clamp conditions, I AHP's were recorded at holding potentials of −50 to −65 mV, following brief depolarization of AH neurons (20–100 ms) to positive potentials (+35 to +50 mV). The null potential of the I AHP at its peak was −89 mV. The AHP and I AHP were largely blocked by ω-conotoxin GVIA (0.6–1 μM). Both events were markedly decreased by caffeine (2–5 mM) and by ryanodine (10–20 μM) added to the bathing solution. Pharmacological suppression of the I AHP with TEA (20 mM) or charybdotoxin (50–100 nM) unmasked an early transient inward current at −55 mV following step depolarization that reversed at −34 mV and was inhibited by niflumic acid (50–100 μM). Mean-variance analysis performed on the decay of the I AHPrevealed that the AHP K+ channels have a mean chord conductance of ∼10 pS, and there are ∼4,000 per AH neuron. Spectral analysis showed that the AHP channels have a mean open dwell time of 2.8 ms. Cell-attached patch recordings from AH neurons confirmed that the channels that open following action currents have a small unitary conductance (10–17 pS) and open with a high probability (≤0.5) within the first 2 s following an action potential. These results indicate that the AHP is largely a consequence of Ca2+ entry through ω-conotoxin GVIA-sensitive Ca2+ channels during the action potential, Ca2+-triggered Ca2+ release from caffeine-sensitive stores and the opening of Ca2+-sensitive small-conductance K+ channels.

scholarly journals Small-conductance calcium-activated potassium (SK) channels contribute to action potential repolarization in human atria

2014 ◽  
Vol 103 (1) ◽  
pp. 156-167 ◽  
Author(s):  
Lasse Skibsbye ◽  
Claire Poulet ◽  
Jonas Goldin Diness ◽  
Bo Hjorth Bentzen ◽  
Lei Yuan ◽  
...  
Keyword(s):  
Action Potential ◽  
Sk Channels ◽  
Action Potential Repolarization ◽  
Small Conductance

scholarly journals Calcium stores regulate excitability in cultured rat hippocampal neurons

2018 ◽  
Vol 120 (5) ◽  
pp. 2694-2705 ◽  
Author(s):  
Menahem Segal
Keyword(s):  
Action Potential ◽  
Hippocampal Neurons ◽  
Extracellular Calcium ◽  
Calcium Stores ◽  
Sk Channels ◽  
Central Neurons ◽  
Action Potential Threshold ◽  
Potential Threshold ◽  
Small Conductance ◽  
Cultured Hippocampal Neurons

Extracellular calcium ions support synaptic activity but also reduce excitability of central neurons. In the present study, the effect of calcium on excitability was explored in cultured hippocampal neurons. CaCl2 injected by pressure in the vicinity of a neuron that is bathed only in MgCl2 as the main divalent cation caused a depolarizing shift in action potential threshold and a reduction in excitability. This effect was not seen if the intracellular milieu consisted of Cs+ instead of K-gluconate as the main cation or when it contained ruthenium red, which blocks release of calcium from stores. The suppression of excitability by calcium was mimicked by caffeine, and calcium store antagonists cyclopiazonic acid or thapsigargin blocked this action. Neurons taken from synaptopodin-knockout mice show significantly reduced efficacy of calcium modulation of action potential threshold. Likewise, in Orai1 knockdown cells, calcium is less effective in modulating excitability of neurons. Activation of small-conductance K (SK) channels increased action potential threshold akin to that produced by calcium ions, whereas blockade of SK channels but not big K channels reduced the threshold for action potential discharge. These results indicate that calcium released from stores may suppress excitability of central neurons. NEW & NOTEWORTHY Extracellular calcium reduces excitability of cultured hippocampal neurons. This effect is mediated by calcium-gated potassium currents, possibly small-conductance K channels. Release of calcium from internal stores mimics the effect of extracellular calcium. It is proposed that calcium stores modulate excitability of central neurons.

scholarly journals Small-conductance Ca2+-activated K+ channels modulate action potential-induced Ca2+ transients in hippocampal neurons

2013 ◽  
Vol 109 (6) ◽  
pp. 1514-1524 ◽  
Author(s):  
Raffaella Tonini ◽  
Teresa Ferraro ◽  
Marisol Sampedro-Castañeda ◽  
Anna Cavaccini ◽  
Martin Stocker ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Apical Dendrite ◽  
Channel Blockers ◽  
Sk Channels ◽  
Hippocampal Pyramidal Neurons ◽  
Voltage Gated ◽  
Small Conductance

In hippocampal pyramidal neurons, voltage-gated Ca2+ channels open in response to action potentials. This results in elevations in the intracellular concentration of Ca2+ that are maximal in the proximal apical dendrites and decrease rapidly with distance from the soma. The control of these action potential-evoked Ca2+ elevations is critical for the regulation of hippocampal neuronal activity. As part of Ca2+ signaling microdomains, small-conductance Ca2+-activated K+ (SK) channels have been shown to modulate the amplitude and duration of intracellular Ca2+ signals by feedback regulation of synaptically activated Ca2+ sources in small distal dendrites and dendritic spines, thus affecting synaptic plasticity in the hippocampus. In this study, we investigated the effect of the activation of SK channels on Ca2+ transients specifically induced by action potentials in the proximal processes of hippocampal pyramidal neurons. Our results, obtained by using selective SK channel blockers and enhancers, show that SK channels act in a feedback loop, in which their activation by Ca2+ entering mainly through L-type voltage-gated Ca2+ channels leads to a reduction in the subsequent dendritic influx of Ca2+. This underscores a new role of SK channels in the proximal apical dendrite of hippocampal pyramidal neurons.

scholarly journals Maternal diabetes increases large conductance Ca2+-activated K+ outward currents that alter action potential properties but do not contribute to attenuated excitability of parasympathetic cardiac motoneurons in the nucleus ambiguus of neonatal mice

2011 ◽  
Vol 300 (5) ◽  
pp. R1070-R1078 ◽  
Author(s):  
Min Lin ◽  
Jeff T. Hatcher ◽  
Qing-Hui Chen ◽  
Robert D. Wurster ◽  
Lihua Li ◽  
...  
Keyword(s):  
Maternal Diabetes ◽  
Bk Channels ◽  
Spike Frequency ◽  
Half Width ◽  
Nucleus Ambiguus ◽  
Whole Cell ◽  
Neonatal Mice ◽  
Outward Currents ◽  
Cell Current ◽  
Diabetic Mothers

Previously, we demonstrated that maternal diabetes reduced the excitability and increased small-conductance Ca2+-activated K+ (SK) currents of parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus (NA). In addition, blockade of SK channels with apamin completely abolished this reduction. In the present study, we examined whether maternal diabetes affects large-conductance Ca2+-activated K+ (BK) channels and whether BK channels contribute to the attenuation of PCMN excitability observed in neonates of diabetic mothers. Neonatal mice from OVE26 diabetic mothers (NMDM) and normal FVB mothers (control) were used. The pericardial sac of neonatal mice at postnatal days 7–9 was injected with the tracer X-rhodamine-5 (and 6)-isothiocyanate 2 days prior to the experiment to retrogradely label PCMNs in the NA. Whole cell current- and voltage-clamps were used to measure spike frequency, action potential (AP) repolarization (half-width), afterhyperpolarization potential (AHP), transient outward currents, and afterhyperpolarization currents ( IAHP). In whole cell voltage clamp mode, we confirmed that maternal diabetes increased transient outward currents and IAHP compared with normal cells. Using BK channel blockers charybdotoxin (CTx) and paxilline, we found that maternal diabetes increased CTx- and paxilline-sensitive transient outward currents but did not change CTx- and paxilline-sensitive IAHP. In whole cell current-clamp mode, we confirmed that maternal diabetes increased AP half-width and AHP, and reduced excitability of PCMNs. Furthermore, we found that after blockade of BK channels with CTx or paxilline, maternal diabetes induced a greater increase of AP half-width but similarly decreased fast AHP without affecting medium AHP. Finally, blockade of BK channels decreased spike frequency in response to current injection in both control and NMDM without reducing the difference of spike frequency between the two groups. Therefore, we conclude that although BK transient outward currents, which may alter AP repolarization, are increased in NMDM, BK channels do not directly contribute to maternal diabetes-induced attenuation of PCMN excitability. In contrast, based on evidence from our previous and present studies, reduction of PCMN excitability in neonates of diabetic mothers is largely dependent on altered SK current associated with maternal diabetes.

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