Tissue-level signaling and control of uterine contractility: the action potential–calcium wave hypothesis

2000 ◽  
Vol 7 (3) ◽  
pp. 146-152 ◽  
Author(s):  
R Young
2011 ◽  
Vol 300 (2) ◽  
pp. H565-H573 ◽  
Author(s):  
Masahide Harada ◽  
Yukiomi Tsuji ◽  
Yuko S. Ishiguro ◽  
Hiroki Takanari ◽  
Yusuke Okuno ◽  
...  

Congestive heart failure (CHF) predisposes to ventricular fibrillation (VF) in association with electrical remodeling of the ventricle. However, much remains unknown about the rate-dependent electrophysiological properties in a failing heart. Action potential properties in the left ventricular subepicardial muscles during dynamic pacing were examined with optical mapping in pacing-induced CHF ( n = 18) and control ( n = 17) rabbit hearts perfused in vitro. Action potential durations (APDs) in CHF were significantly longer than those observed for controls at basic cycle lengths (BCLs) >1,000 ms but significantly shorter at BCLs <400 ms. Spatial APD dispersions were significantly increased in CHF versus control (by 17–81%), and conduction velocity was significantly decreased in CHF (by 6–20%). In both groups, high-frequency stimulation (BCLs <150 ms) always caused spatial APD alternans; spatially concordant alternans and spatially discordant alternans (SDA) were induced at 60% and 40% in control, respectively, whereas 18% and 82% in CHF. SDA in CHF caused wavebreaks followed by reentrant excitations, giving rise to VF. Incidence of ventricular tachycardia/VFs elicited by high-frequency dynamic pacing (BCLs <150 ms) was significantly higher in CHF versus control (93% vs. 20%). In CHF, left ventricular subepicardial muscles show significant APD shortenings at short BCLs favoring reentry formations following wavebreaks in association with SDA. High-frequency excitation itself may increase the vulnerability to VF in CHF.


1990 ◽  
Vol 258 (3) ◽  
pp. H793-H805 ◽  
Author(s):  
F. S. Fein ◽  
B. E. Zola ◽  
A. Malhotra ◽  
S. Cho ◽  
S. M. Factor ◽  
...  

Left ventricular papillary muscle function, transmembrane action potentials, myosin adenosinetriphosphatase (ATPase) and isoenzyme distribution, and myocardial pathology were studied in hypertensive (H), diabetic (D), hypertensive-diabetic (HD), and control (C) rats. There was approximately 50% relative left ventricular hypertrophy in H and HD rats. Relative lung and liver weights were greater in HD rats. Peak velocity of shortening tended to decrease progressively in H, D, and HD rats. The duration of contraction and relaxation was markedly prolonged in Ds and HDs. The length-developed tension relation was blunted in HDs. The negative inotropic effect of verapamil was similar in all groups. Resting membrane potential and amplitude were decreased in D and HD rats. Action potential duration was increased in H, D, and especially HD rats. The shortening of action potential duration with increased stimulus frequency was greater in H, D, and especially HD rats than in Cs. Left ventricular myosin ATPase and V1 isoenzyme content decreased progressively in H, D, and HD rats. Right ventricular V1 isoenzyme content was not affected in H rats but was markedly decreased in D and HD rats. Left (and right) ventricular pathology was unchanged in rats with diabetes but was increased in rats with hypertension. These data suggest that the combination of myocardial pathology (due to hypertension) and cellular dysfunction (caused mainly by diabetes) may result in cardiomyopathy and congestive heart failure in the HD rat.


2021 ◽  
Vol 61 (1) ◽  
pp. 381-400
Author(s):  
Emely Thompson ◽  
Jodene Eldstrom ◽  
David Fedida

Kv7 channels (Kv7.1–7.5) are voltage-gated K+ channels that can be modulated by five β-subunits (KCNE1–5). Kv7.1-KCNE1 channels produce the slow-delayed rectifying K+ current, IKs, which is important during the repolarization phase of the cardiac action potential. Kv7.2–7.5 are predominantly neuronally expressed and constitute the muscarinic M-current and control the resting membrane potential in neurons. Kv7.1 produces drastically different currents as a result of modulation by KCNE subunits. This flexibility allows the Kv7.1 channel to have many roles depending on location and assembly partners. The pharmacological sensitivity of Kv7.1 channels differs from that of Kv7.2–7.5 and is largely dependent upon the number of β-subunits present in the channel complex. As a result, the development of pharmaceuticals targeting Kv7.1 is problematic. This review discusses the roles and the mechanisms by which different signaling pathways affect Kv7.1 and KCNE channels and could potentially provide different ways of targeting the channel.


1989 ◽  
Vol 67 (12) ◽  
pp. 1471-1479 ◽  
Author(s):  
C. Thollon ◽  
P. Kreher

We investigated the electrophysiological effects of cardiac hypertrophy induced by different experimental models. Comparison of the action potentials of hypertrophied and control rat hearts reveals a pronounced prolongation of the action potential for all types of hypertrophy. This prolongation affects the entire repolarization phase of the action potential 8 days after severe aortic constriction, after 8 days of isoproterenol treatment (5 mg/kg per day), and 3 months after an aortocaval fistula. The electrical changes associated with myocardial hypertrophy induced by pressure overload (aortic constriction) were compared with those resulting from volume overload (aortocaval fistula). Our results show that action potential alterations depend on the nature, duration, and severity of the work load. Thus, pressure overload is more potent to induce these modifications. In the hearts subjected to pressure overload, action potential alterations appear more rapidly and are more marked for the same degree of hypertrophy than those of the volume-hypertrophied myocardium. Furthermore, such data also demonstrate that the early alteration of the action potential during the development of compensatory hypertrophy is a prolongation of the later phase of repolarization (phase 3), without prolongation of the other repolarization phases (1 and 2). This change appears 3 days after aortic constriction, 1 month after coronary artery ligation (in the healthy part of the left ventricle), and 1 month after an aortocaval fistula. In the rat heart, the ionic currents underlying this later phase of repolarization are known to be dependent on the increase of intracellular free calcium during activity. Since this elevation of myoplasmic calcium results from calcium release from the sarcoplasmic reticulum, we compared the effects of caffeine (a substance known to act on the sarcoplasmic reticulum) on the electrical events of hypertrophied and control hearts. Caffeine has a different qualitative effect in hypertrophied and control hearts. The results suggest that hypertrophy should be due to increased calcium release from the sarcoplasmic reticulum related to increased phosphoinositide hydrolysis and therefore that the prolongation of the action potential duration (phase 3) may be the result of an increase of the Na–Ca exchange current or of a specific suppression of the outward K+ current.Key words: aortic stenosis, isoproterenol treatment, coronary artery ligation, aortocaval fistula, action potential, caffeine.


BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qingping Wang ◽  
Hong Chu ◽  
Hongyang Wang ◽  
Yan Jin ◽  
Xiaoquan Zhao ◽  
...  

Abstract Objective To explore the sensitivity of median and ulnar nerve sensory latency differences in diagnosing carpal tunnel syndrome (CTS) at different severities. Methods CTS patients were divided into three groups based on disease severity (mild, moderate, and severe). Distal latency of sensory nerve action potential (SNAP) for the median and ulnar nerves was recorded. The sensitivity of SNAP distal latency to CTS and its correlation with CTS severity were analyzed. Results Significant differences were found in the median nerve sensory action potential distal latency (MSDL) and in the median and ulnar sensory latency difference to ring finger (MUD) but not in the ulnar nerve sensory action potential distal latency (USDL) between CTS and control. The sensitivity and specificity were 92.2 and 99.4% with an MSDL cutoff value of 2.40 ms, respectively, and were both 100% with a MUD cutoff value of 0.33 ms. There was no significant difference in USDL among the CTS and control groups. Significant differences were found in MSDL and MUD among the CTS severities and between mild and moderate CTS, but not between mild and severe CTS or between moderate and severe CTS. Correlations with CTS severity were observed for MSDL and MUD but not for USDL. Conclusion The ulnar nerve of the CTS patients was not damaged. A smaller MSDL reflected median nerve damage, which can be used for the early diagnosis of CTS. MUD correlated with CTS severity with a higher sensitivity than MSDL, which can provide therapeutic insight without pain to patients.


Author(s):  
Xiaopeng Zhao

Cardiac alternans is an initiator of ventricular fibrillation, a fatal heart rhythm disorder that kills hundreds of thousands people in the US each year. Alternans manifests as a pattern with beat-to-beat long-short variations in action potential duration. In an isolated cardiac cell, alternans arises as a supercritical period-doubling bifurcation. In cardiac tissue (coupled cells), propagation effect leads to more complicated bifurcation structures. Specifically, there may coexist multiple spatiotemporal patterns of alternans in tissue due to the interaction between electrotonic coupling and intrinsic instability in the dynamics of action potential. In this work, we carry out a detailed bifurcation analysis to illustrate the mechanism that leads to this phenomenon. The results on this analysis may shed light on the onset and control of the dreadful instability of cardiac alternans.


2004 ◽  
Vol 91 (1) ◽  
pp. 571-575 ◽  
Author(s):  
Jason J. Kuo ◽  
Martijn Schonewille ◽  
Teepu Siddique ◽  
Annet N. A. Schults ◽  
Ronggen Fu ◽  
...  

ALS (amyotrophic lateral sclerosis) is an adult-onset and deadly neurodegenerative disease characterized by a progressive and selective loss of motoneurons. Transgenic mice overexpressing a mutated human gene (G93A) coding for the enzyme SOD1 (Cu/Zn superoxide dismutase) develop a motoneuron disease resembling ALS in humans. In this generally accepted ALS model, we tested the electrophysiological properties of individual embryonic and neonatal spinal motoneurons in culture by measuring a wide range of electrical properties influencing motoneuron excitability during current clamp. There were no differences in the motoneuron resting potential, input conductance, action potential shape, or afterhyperpolarization between G93A and control motoneurons. The relationship between the motoneuron's firing frequency and injected current (f-I relation) was altered. The slope of the f-I relation and the maximal firing rate of the G93A motoneurons were much greater than in the control motoneurons. Differences in spontaneous synaptic input were excluded as a cause of increased excitability. This finding identifies a markedly elevated intrinsic electrical excitability in cultured embryonic and neonatal mutant G93A spinal motoneurons. We conclude that the observed intrinsic motoneuron hyperexcitability is induced by the SOD1 toxic gain-of-function through an aberration in the process of action potential generation. This hyperexcitability may play a crucial role in the pathogenesis of ALS as the motoneurons were cultured from presymptomatic mice.


Author(s):  
Edgard El Chaar ◽  
Algirdas Puisys ◽  
Itai Sabbag ◽  
Benjamin Bellón ◽  
Aikaterini Georgantza ◽  
...  

Abstract Objectives To assess the osseointegration and crestal bone level maintenance of a novel fully tapered self-cutting tissue-level implant for immediate placement (test) compared to a clinically established tissue-level implant (control) in moderate bone quality. Materials and methods Test and control implants were compared in 3 groups, i.e., small-, medium-, and large-diameter implants in an edentulous mandibular minipig model with moderate bone quality after 12 weeks of healing. Histometrically derived bone-to-implant contact (BIC) and first bone-to-implant contact (fBIC) were subjected to statistical non-inferiority testing. Maximum insertion torque values in artificial bone were assessed for comparison. Results BIC values for the tests and control implants for all 3 diameters were comparable and non-inferior: small diameter (61.30 ± 10.63% vs. 54.46 ± 18.31%) (p=0.99), medium diameter (60.91 ± 14.42 vs. 54.68 ± 9.16) (p=0.55), and large diameter (45.60 ± 14.67 vs. 52.52 ± 14.76) (p=0.31). fBIC values for test implants were higher and non-inferior compared to control implants in all three groups. Test implants further showed distinctly higher maximum insertion torque values compared to control implants. Conclusion The investigated novel tissue-level implant is able to achieve high levels of primary and secondary implant stability under simultaneous preservation of crestal bone levels. This qualifies the studied implant as an attractive candidate for immediate placement in bone of limited quality. Clinical relevance This pilot pre-clinical study investigated a novel tissue-level implant for immediate placement. With the aim of translating the studied prototype into clinical application pre-clinical models, procedures and controls have been chosen with the aim of reflecting its future clinical indication and use.


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