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Idiopathic Ventricular Tachycardia
Published in Andrea Natale, Oussama M. Wazni, Kalyanam Shivkumar, Francis E. Marchlinski, Handbook of Cardiac Electrophysiology, 2020
Jackson J. Liang, David S. Frankel
Long-term medical management Calcium channel blockers are most effective, followed by beta blockers and potassium channel blockers. Sodium channel blockers are least effective.
Arterial Baroreceptors: Excitation and Modulation
Published in Irving H. Zucker, Joseph P. Gilmore, Reflex Control of the Circulation, 2020
Diana L. Kunze, Michael C. Andresen
The way in which the baroreceptor ending responds to pressure or distortion is thought to be by the development of a receptor or generator potential (Fig. 10). Like many other mechanoreceptors, stretch of baroreceptors probably activates a relatively nonselective membrane conductance to cations (Grigg, 1986). Matsuura (1973) recorded a tetrodotoxin-insensitive, slow potential from common carotid baroreceptors that was Na+-dependent and fit several criteria for a generator potential. Involvement of particular ions in the generation of the receptor potential were inferred from recordings of baroreceptor spike trains when the ionic environment was manipulated. Decreases in extracellular Na+ increased threshold pressures and decreased gain (Saum et al., 1977); findings consistent with Na+ entry during excitation (Fig. 11a). Increases in external K+ had the opposite effects evidently as a result of changes in membrane potential (Fig. 11b). Experiments changing external Ca2+ and with a variety of calcium channel blockers (organic, inorganic and dihydropyridine) were consistent with a Ca2+ surface charge effect (Frankenhauser and Hodgkin, 1957) and opposite to that expected if calcium entry contributed substantially to the excitatory depolarization (Andresen and Kunze, 1987). Substitution of impermeant anions for chloride did not affect baroreceptor discharge (Saum et al., 1977). Overall, the data suggest that distortion of baroreceptor receptive fields causes an increase in membrane conductance primarily to monovalent cations. Studies in other preparations have shown that some cells do contain ionic channels that respond to stretch of the membrane (Sachs, 1987). Although most of the original studies were done on myelinated fibers, the results have been confirmed in unmyelinated fibers (Thorén et al., 1982). Further characterization of the presence of particular ion channels in the terminal has been sought by using ion channel blockers. The potassium channel blocker 4-aminopyridine has been used to infer the presence of a specific potassium channel (Gallenberg et al., 1989). Calcium channel blockers have been used to infer the presence of voltage-dependent calcium channels. There are conflicting results concerning their presence from different laboratories (Heesch et al., 1983; Kunze et al., 1986). Most of these agents are not specific for a particular ion channel, particularly over all concentration ranges. Thus these indirect observations must be considered with caution in the absence of more direct measures of the ionic current of interest.
New methodological approaches to atrial fibrillation drug discovery
Published in Expert Opinion on Drug Discovery, 2021
For trans-membrane ion channel blockers, there is a trend toward developing sodium and potassium channel blockers with atrial-specific actions to minimize ventricular side effects. The benefits of concurrently blocking multiple ions to achieve synergistic antiarrhythmic effects and minimize adverse effects have also been long recognized. Vernakalant, an AAD with primary action against sodium and potassium channels, is effective in pharmacological cardioversion of AF. Combination therapies with ranolazine, amiodarone, and its derivatives have also been shown to be efficacious. [32,33] Nonetheless the optimal dosage of different agents in these combinations and the potential long-term adverse effects of these ‘shotgun approaches,’ such as QT prolongation, remain major barriers to testing this type of nonselective combination therapy in larger randomized controlled trials. In future, it will be preferable to adopt a more tailored approach and have more specific combinations of selective compounds in different populations to improve the safety and efficacy of a combination of antiarrhythmic agents for AF.
The potassium channel blocker, dalfampridine diminishes ouabain-induced arrhythmia in isolated rat atria
Published in Archives of Physiology and Biochemistry, 2019
Nahid Ghebleh Zadeh, Gholamhassan Vaezi, Azam Bakhtiarian, Zahra Mousavi, Abdolhossein Shiravi, Vahid Nikoui
Potassium (K+) channels are the main type of ion channel and are distributed in all living organisms (Littleton and Ganetzky 2000). These channels make potassium-selective pores that located inside cell membranes. Moreover, these channels are localized on various cell types and regulate numerous cellular functions (Schmitt et al. 2014). These channels also control the repolarization of atrial action potentials (Schmitt et al. 2014). It is well-known that prolongation of cardiac action potential and effective refractory period prevents cardiac arrhythmias, particularly in short action potential conditions. Recent investigations are focused on discovering the antiarrhythmic agents the prolong action potentials without proarrhythmic adverse effects. As well as sodium channel blockers, potassium channel blockers also exert antiarrhythmic properties (Gerlach 2003). Based on Vaughan-Williams classification scheme, potassium channel blockers are class III antiarrhythmic agents. These agents block the potassium channels, which mediate phase 3 of repolarization. Consequently, blockade of these channels delays repolarization, which prolongs both action potential duration and effective refractory period (Singh and Ahmed 1994, Dorian 2000).
Altered Potassium Ion Channel Function as a Possible Mechanism of Increased Blood Pressure in Rats Fed Thermally Oxidized Palm Oil Diets
Published in Journal of Dietary Supplements, 2018
Etah E. Nkanu, Daniel U. Owu, Eme E. Osim
This study examined the effect of long-term ingestion of two forms of palm oil on blood pressure and the possible role of potassium ion channel in blood pressure regulation. In this study, potassium channel blockers and openers were used to determine the mechanism of arterial blood pressure changes, since these channels play a vital role in the modulation of vascular tone (Gutterman, Miura, & Liu, 2005). The results show a significant increase in basal MAP in the TPO group and a decrease in MAP in the FPO-treated group compared to control. This is in agreement with previous studies on the effect of a palm oil diet on blood pressure (Osim, Owu, & Etta, 1996; Leong et al., 2009). It is interesting to note that injection of levcromakalim, a KATP channel opener, caused about 37% decrease in MAP in the FPO group and about 12% decrease in MAP in the TPO group. These findings suggest that potassium ion channel plays a role in the regulation of blood pressure. It, therefore, suggests that KATP channel opening may be one of the possible mechanisms of reduction of MAP by FPO.