scholarly journals Physical basis for distinct basal and mechanically-gated activity of the human K+ channel TRAAK

2021 ◽  
Author(s):  
Robert A Rietmeijer ◽  
Em Sorum ◽  
Baobin Li ◽  
Stephen G. Brohawn

TRAAK is a mechanosensitive two-pore domain K+ (K2P) channel localized to nodes of Ranvier in myelinated neurons. TRAAK deletion in mice results in mechanical and thermal allodynia and gain-of-function mutations cause the human neurodevelopmental disorder FHEIG. TRAAK displays basal and stimulus-gated activities typical of K2Ps, but the mechanistic and structural differences between these modes are unknown. Here, we demonstrate that basal and mechanically-gated openings are distinguished by their conductance, kinetics, and structure. Basal openings are low conductance, short duration, and occur through a channel with an interior cavity exposed to the surrounding membrane. Mechanically-gated openings are high conductance, long duration, and occur through a channel that is sealed to the surrounding membrane. Our results explain how dual modes of activity are produced by a single ion channel and provide a basis for the development of state-selective pharmacology with the potential to treat disease.

2016 ◽  
Vol 130 (9) ◽  
pp. 643-650 ◽  
Author(s):  
Felix Wiedmann ◽  
Constanze Schmidt ◽  
Patrick Lugenbiel ◽  
Ingo Staudacher ◽  
Ann-Kathrin Rahm ◽  
...  

Key words: anti-arrhythmic therapy, arrhythmia, atrial fibrillation, ion channel, K2P channel, TWIK-related acid-sensitive K+ channel 1 (TASK-1).


Author(s):  
Omar J Guerra ◽  
Joshua Eichman ◽  
Paul Denholm

Achieving 100% carbon-free or renewable power systems can be facilitated by the deployment of energy storage technologies at all timescales, including short-duration, long-duration, and seasonal scales; however, most current literature...


2010 ◽  
Vol 98 (3) ◽  
pp. 227a
Author(s):  
Jorg Grandl ◽  
Sung Eun Kim ◽  
Valerie Uzzell ◽  
Badry Bursulaya ◽  
Matt Petrus ◽  
...  

1989 ◽  
Vol 62 (6) ◽  
pp. 1225-1236 ◽  
Author(s):  
S. M. Gurahian ◽  
S. H. Chandler ◽  
L. J. Goldberg

1. The effects of repetitive stimulation of the nucleus pontis caudalis and nucleus gigantocellularis (PnC-Gi) of the reticular formation on jaw opener and closer motoneurons were examined. The PnC-Gi was stimulated at 75 Hz at current intensities less than 90 microA. 2. Rhythmically occurring, long-duration, depolarizing membrane potentials in jaw opener motoneurons [excitatory masticatory drive potential (E-MDP)] and long-duration hyperpolarizing membrane potentials [inhibitory masticatory drive potentials (I-MDP)] in jaw closer motoneurons were evoked by 40-Hz repetitive masticatory cortex stimulation. These potentials were completely suppressed by PnC-Gi stimulation. PnC-Gi stimulation also suppressed the short-duration, stimulus-locked depolarizations [excitatory postsynaptic potentials (EPSPs)] in jaw opener motoneurons and short-duration, stimulus-locked hyperpolarizations [inhibitory postsynaptic potentials (IPSPs)] in jaw closer motoneurons, evoked by the same repetitive cortical stimulation. 3. Short pulse train (3 pulses; 500 Hz) stimulation of the masticatory area of the cortex in the absence of rhythmical jaw movements activated the short-latency paucisynaptic corticotrigeminal pathways and evoked short-duration EPSPs and IPSPs in jaw opener and closer motoneurons, respectively. The same PnC-Gi stimulation that completely suppressed rhythmical MDPs, and stimulus-locked PSPs evoked by repetitive stimulation to the masticatory area of the cortex, produced an average reduction in PSP amplitude of 22 and 17% in jaw closer and opener motoneurons, respectively. 4. PnC-Gi stimulation produced minimal effects on the amplitude of the antidromic digastric field potential or on the intracellularly recorded antidromic digastric action potential. Moreover, PnC-Gi stimulation had little effect on jaw opener or jaw closer motoneuron membrane resting potentials in the absence of rhythmical jaw movements (RJMs). PnC-Gi stimulation produced variable effects on conductance pulses elicited in jaw opener and closer motoneurons in the absence of RJMs. 5. These results indicate that the powerful suppression of cortically evoked MDPs in opener and closer motoneurons during PnC-Gi stimulation is most likely not a result of postsynaptic inhibition of trigeminal motoneurons. It is proposed that this suppression is a result of suppression of activity in neurons responsible for masticatory rhythm generation.


1990 ◽  
Vol 26 (1) ◽  
pp. 63-72 ◽  
Author(s):  
R. C. Nageswara Rao ◽  
K. D. R. Wadia ◽  
J. H. Williams

SUMMARYThree short duration and one long duration groundnut genotypes, grown either ‘sole’ or as intercrops (in 1:1 ratios of the short duration with the long duration genotypes), were compared in four trials. The intercrop treatments resulted in Land Equivalent Ratios (LERs) of up to 1.25 for pod yield and total biomass despite moderate or severe water deficits at the end of the season. Specific combinations of genotypes were necessary to maximize the LER. The results indicate there is scope for achieving greater productivity in environments with a variable season length by growing late and early genotypes together in an intercrop system.


2013 ◽  
Vol 110 (4) ◽  
pp. 984-998 ◽  
Author(s):  
Wilsaan M. Joiner ◽  
Jordan B. Brayanov ◽  
Maurice A. Smith

The way that a motor adaptation is trained, for example, the manner in which it is introduced or the duration of the training period, can influence its internal representation. However, recent studies examining the gradual versus abrupt introduction of a novel environment have produced conflicting results. Here we examined how these effects determine the effector specificity of motor adaptation during visually guided reaching. After adaptation to velocity-dependent dynamics in the right arm, we estimated the amount of adaptation transferred to the left arm, using error-clamp measurement trials to directly measure changes in learned dynamics. We found that a small but significant amount of generalization to the untrained arm occurs under three different training schedules: a short-duration (15 trials) abrupt presentation, a long-duration (160 trials) abrupt presentation, and a long-duration gradual presentation of the novel dynamic environment. Remarkably, we found essentially no difference between the amount of interlimb generalization when comparing these schedules, with 9–12% transfer of the trained adaptation for all three. However, the duration of training had a pronounced effect on the stability of the interlimb transfer: The transfer elicited from short-duration training decayed rapidly, whereas the transfer from both long-duration training schedules was considerably more persistent (<50% vs. >90% retention over the first 20 trials). These results indicate that the amount of interlimb transfer is similar for gradual versus abrupt training and that interlimb transfer of learned dynamics can occur after even a brief training period but longer training is required for an enduring effect.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Julia H Indik ◽  
Mathias Zuercher ◽  
Karl B Kern ◽  
Ronald W Hilwig ◽  
Robert A Berg

It is known that defibrillation of ventricular fibrillation (VF) to a perfusing rhythm (ROSC) is more likely to occur in VF of short duration. It is unknown whether ROSC can be predicted by waveform characteristics in VF of short compared to long duration, apart from a consideration of time alone. VF was untreated for 2 minutes (N=10) or 8 minutes (N=10) in normal swine, after which a defibrillation shock was applied. Chest compressions for two minutes were allowed following but not prior to the shock to achieve a perfusing rhythm (ROSC). VF was analyzed from needle electrodes prior to the shock for amplitude spectral area (AMSA), slope, median frequency and bandwidth. Predictors of ROSC were determined by logistic regression. In VF of 2 minute duration 7 out of 10 swine achieved ROSC compared to 2 out 10 swine with VF of 8 minutes (P=0.025) and time was a significant predictor of ROSC (P=0.033). AMSA was significantly higher at 2 minutes (75 ± 18 mV-Hz) compared to 8 minutes (56±11 mV-Hz, p=0.007) as was slope (3.5±1 vs 2.6±0.5 mV/s, p=0.015). Bandwidth was slightly increased from 2.2±0.6 Hz at 2 minutes to 2.8±0.8 Hz at 8 minutes,(p=0.048), while median frequency was similar. However, no waveform characteristic was a significant predictor of ROSC, with substantial overlap in distributions between animals with and without ROSC. Duration of VF is an important determinant of the likelihood of achieving ROSC with defibrillation. Particularly in VF of short duration, VF waveform characteristics do not add to the predictability of achieving ROSC even though they may demonstrate a significant time evolution.


1998 ◽  
Vol 274 (3) ◽  
pp. E397-E402 ◽  
Author(s):  
Michael C. Hogan ◽  
Erica Ingham ◽  
S. Sadi Kurdak

It has been suggested that during a skeletal muscle contraction the metabolic energy cost at the onset may be greater than the energy cost related to holding steady-state force. The purpose of the present study was to investigate the effect of contraction duration on the metabolic energy cost and fatigue process in fully perfused contracting muscle in situ. Canine gastrocnemius muscle ( n = 6) was isolated, and two contractile periods (3 min of isometric, tetanic contractions with 45-min rest between) were conducted by each muscle in a balanced order design. The two contractile periods had stimulation patterns that resulted in a 1:3 contraction-to-rest ratio, with the difference in the two contractile periods being in the duration of each contraction: short duration 0.25-s stimulation/0.75-s rest vs. long duration 1-s stimulation/3-s rest. These stimulation patterns resulted in the same total time of stimulation, number of stimulation pulses, and total time in contraction for each 3-min period. Muscle O2 uptake, the fall in developed force (fatigue), the O2 cost of developed force, and the estimated total energy cost (ATP utilization) of developed force were significantly greater ( P < 0.05) with contractions of short duration. Lactate efflux from the working muscle and muscle lactate concentration were significantly greater with contractions of short duration, such that the calculated energy derived from glycolysis was three times greater in this condition. These results demonstrate that contraction duration can significantly affect both the aerobic and anaerobic metabolic energy cost and fatigue in contracting muscle. In addition, it is likely that the greater rate of fatigue with more rapid contractions was a result of elevated glycolytic production of lactic acid.


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