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The heart
Published in Laurie K. McCorry, Martin M. Zdanowicz, Cynthia Y. Gonnella, Essentials of Human Physiology and Pathophysiology for Pharmacy and Allied Health, 2019
Laurie K. McCorry, Martin M. Zdanowicz, Cynthia Y. Gonnella
The effective refractory period is followed by a relative refractory period that lasts for the remaining 50 ms of the ventricular action potential. During this period, action potentials may be generated; however, the myocardium is more difficult than normal to excite.
Ventricular myocyte electrophysiology
Published in Burt B. Hamrell, Cardiovascular Physiology, 2018
The plateau portion of the ventricular action potential is important for two major reasons: Fast Na+ channels remain inactivated during the plateau. The transmembrane potential during the plateau hovers at close to 0 mV. Na+ channels remain inactivated at this transmembrane voltage and normally another action potential cannot be induced. This accounts for the long duration of refractoriness in ventricular myocytes. The long duration of refractoriness prevents extra depolarizations from occurring.Intracellular Ca2+ concentration increases. The small amount of Ca2+ that enters through the L-type sarcolemmal channels during the plateau triggers release of substantial amounts of Ca2+ from the terminal cisternae of the sarcoplasmic reticulum. This Ca2+-induced-Ca2+-release results in the large increase in cytoplasmic Ca2+ that initiates contraction. This small inward movement of Ca2+ and the significant increase in internal Ca2+ concentration due to Ca2+-induced-Ca2+-release is an exception to the rule that during an action potential there are no measurable changes in ionic concentrations.
Electrical Properties of the Heart
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Ventricular muscle action potentials are longer in duration and have a distinct plateau phase during which depolarization is maintained (Figure 24.4). The resting membrane potential of cardiac muscle is about −85 to −95 mV, and the action potential is 105 mV. The membranes are depolarized for 0.2 s in the atria and for 0.3 s in the ventricles. Phase 0 (depolarization). The ventricular muscle cell is depolarized by a rise in sodium permeability. Fast sodium channels open for only a few ten-thousandths of a second, and a fast sodium current (iNa) produces rapid depolarization. These are similar to those in nerves and are sensitive to tetrodotoxin. Potassium conductance decreases.Phase 1 (partial repolarization). Two processes terminate depolarization: (i) a rapid decrease in sodium permeability when the inactivation gates in the fast sodium channels close and (ii) voltage-sensitive transient outward (ITO) potassium channels open, allowing potassium ions to diffuse out of the cell down a concentration gradient.Phase 2 (plateau phase). During the plateau phase, there is a long period (150–200 ms) of a relatively stable depolarized membrane potential, a feature unique to the ventricular action potential. Depolarization due to the fast sodium channels increases the permeability to Ca++ ions by opening the L-type calcium channels, allowing Ca++ ions to enter the cell down a concentration gradient. Membrane potential during this plateau phase is relatively constant because the inward flow of Ca++ ions is balanced by an equal but outward flow of K+ ions.Phase 3 (repolarization phase). The plateau phase is terminated by the closure of the L-type calcium channels and an increase in outward potassium current, the delayed rectifier potassium current (IKr). At the end of phase 3, repolarization brings the membrane potential closer to the equilibrium potential of K+.Phase 4 (resting potential). The membrane potential returns to the resting level of –85 mV. The membrane is stable as the inward and outward currents are equal. The outward potassium current balances the inward calcium and sodium currents.
Effect of allisartan on blood pressure and left ventricular hypertrophy through Kv1.5 channels in hypertensive rats
Published in Clinical and Experimental Hypertension, 2022
Chunfang Xu, Ziying Zhao, Wang Yuan, Zhao Fengping, Yan Zhiqiang, Zhang Xiaoqin
Allisartan is a newly developed selective nonpeptide sartan type ARB. Unlike losartan, allisartan is directly converted to EXP3174 by esterase hydrolysis in gastrointestinal tract even in the absence of CYP450. Thus, reducing total number of metabolites in plasma makes allisartan safer and more tolerable compared to losartan (3,5). Wu et al. reported allisartan to be highly effective and less toxic in animal models (4). Myocardial remodeling is characterized by complex signaling network like loss of myocyte, hypertrophy, mitochondrial dysfunction, metabolic abnormalities, fibrosis, and alteration of extracellular matrix homeostasis (15). Of these, alteration of extracellular matrix homeostasis plays an important role in remodeling. Continuous association of LVH with prolongation of ventricular action potentials and alterations in the dispersion of repolarization, LVH results in electrophysiological instability. These electrical imbalance leads to alterations in the functioning of the K+ channels that trigger ventricular action potential repolarization. Of all potassium channels, voltage-gated potassium channels (Kvs) are the largest and most diverse with many biological functions (16). Of these, Kv1.5 was reported to be expressed in vascular smooth muscle cells and ventricles while downregulated in hypertrophied ventricle and also plays an important role in regulation of membrane potential (17–19). Hence, the present study was designed to evaluate the effects of allisartan on blood pressure (BP) and left ventricular hypertrophy through Kv1.5 channels.
Pinocembrin ameliorates arrhythmias in rats with chronic ischaemic heart failure
Published in Annals of Medicine, 2021
Yan Guo, Cui Zhang, Tianxin Ye, Xiuhuan Chen, Xin Liu, Xiaoli Chen, Yazhou Sun, Chuan Qu, Jinjun Liang, Shaobo Shi, Bo Yang
There are some limitations in this study. First, there are many ion channels that affect the plateau phase. We pay more attention to Ito and ICa-L. However, although the Ito and ICa-L are dominant currents in the repolarization period for both humans and rats, the effect of Ito in rats is significantly greater than that in humans. In addition, the delayed rectifier K current and the INa/Ca are both the important repolarization currents that affect the human ventricular action potential, which may not be obvious in rat ventricular myocytes. The further studies required. Second, inflammatory responses and oxidative stress can also lead to adverse cardiac outcomes, which needs more subsequent studies. Finally, we focus on the inhibitory effect of pinocembrin on VAs, and its effect on the SHAM group may requires further evaluation. Nevertheless, we still provide a potential target for the treatment of CIHF and VAs.
Effects of antiarrhythmics and hypokalemia on the rate adaptation of cardiac repolarization
Published in Scandinavian Cardiovascular Journal, 2018
It remains incompletely understood as to whether the rate adaptation of ventricular repolarization can be adversely modified by drugs that facilitate arrhythmia, in comparison to the agents with safe therapeutic profiles. In this regard, one particular example are Na+ channel blockers, which include both clinically safe class Ib agents (such as lidocaine) and the drugs known to increase propensity for ventricular tachyarrhythmia (VT) in susceptible patients, such as class Ia (e.g. quinidine, procainamide) and class Ic agents (flecainide) [9–11]. The striking differences in the safety profile among class I agents are likely attributed to their dissimilar effects at the ion channel level – whilst lidocaine is a selective INa blocker, quinidine, procainamide, and flecainide show more complex effects that include both INa blockade and inhibition of repolarizing K+ currents, such as the delayed rectifier (IK), in cardiac cells [9,10]. The latter can potentially contribute to repolarization abnormalities, including the slowed rate adaptation of ventricular action potential duration, which would partly account for the adverse drug effects. In support of this notion, flecainide, class Ic agent with clinically documented arrhythmogenic effects [10,11], has been shown to attenuate the rate adaptation of repolarization in perfused guinea-pig heart model [12]. Furthermore, the clinical studies suggest that QT shortening in exercise-induced tachycardia is attenuated in patients with a history of VT induced by class Ia antiarrhythmics [13].