The membrane permeability to potassium at a resting state is greater than to any other ions and the maintenance of resting membrane potential is largely dependent on K+ concentration of outside medium (Hodgkin and Horowicz 1959), i.e. an increase of K+ concentration of medium induces a depolarization, vice versa. However, on the contrary to this prediction, in some mammalian heart muscle a reduction of external K+ concentration induces a depolarization of membrane potential rather than a hyperpolarization (Vassalle 1965). In this study it was aimed to elucidate the possible mechanism of spontaneous depolarization induced by low external K+ in canine Purkinje fibers. The membrane potential was constantly recorded while components of cations in the bathing medium were replaced one by one by equimolar sucrose until the low K+ induced depolarization was blocked. The results are summarized as follows; The membrane potential of canine Purkinje fibers was spontaneously depolarized by low external K+, and the magnitude of depolarization was not affected by verapamil TEA, and a partial replacement of external Na+ and Ca2+ with choline chloride. But the membrane potential was hyperpolarized only when the all external cations were substitued with sucrose; and this hyperpolarization was disappeared again by substitution of sucrose with choline chloride. From these results, it may be concluded that the depolarization induced by low external K+ in canine Purkinje fibers is due to the nonspecific increase of membrane permeability to external cations and/or combinations with decreased K+ conductance.
Animal ; Dogs ; Guinea Pigs ; Heart/physiology* ; Membrane Potentials/drug effects* ; Papillary Muscles/physiology ; Potassium/pharmacology* ; Purkinje Fibers/physiology ; Rest

Action Potentials ; drug effects ; Calcium Channel Blockers ; pharmacology ; Cinnarizine ; analogs & derivatives ; pharmacology ; Heart Atria ; Humans ; Isoproterenol ; antagonists & inhibitors ; Microelectrodes ; Purkinje Fibers ; drug effects ; physiology

PURPOSE: We hypothesized that Purkinje potential and their preferential conduction to the left ventricle (LV) posteroseptum during sinus rhythm (SR) are part of reentrant circuits of idiopathic left ventricular tachycardia (ILVT) and reentry anchors to papillary muscle. MATERIALS AND METHODS: In 14 patients with ILVT (11 men, mean age 31.5+/-11.1 years), we compared Purkinje potential and preferential conduction during SR with VT by non-contact mapping (NCM). If clear Purkinje potential(SR) was observed in the LV posteroseptum and the earliest activation site (EA) of preferential conduction at SR (EASR) was well matched with that of VT (EAVT), EASR was targeted for radiofrequency catheter ablation (RFCA). Also, the anatomical locations of successful ablation sites were evaluated by echocardiography in five additional patients. RESULTS: 1) All induced VTs exhibited clear Purkinje potential(VT) and preferential conduction in the LV posteroseptum. The Purkinje potential(VT) and EAVT was within 5.8+/-8.2 mm of EASR. However, the breakout sites of VT were separated by 30.2+/-12.6 mm from EAVT to the apical side. 2) Purkinje potential(SR) demonstrated a reversed polarity to Purkinje potential(VT), and the interval of Purkinje potential(SR)-QRS was longer than the interval of Purkinje potential(VT)-QRS (p<0.02) 3) RFCA targeting EASR eliminated VT in all patients without recurrence within 23.3+/-7.5 months, and the successful ablation site was discovered at the base of papillary muscle in the five additional (100%) patients. CONCLUSION: NCM-guided localization of EASR with Purkinje potential(SR) matches well with EAVT with Purkinje potential(VT) and provides an effective target for RFCA, potentially at the base of papillary muscle in patients with ILVT.
Adult ; Catheter Ablation ; Electrophysiology ; Female ; Humans ; Male ; Purkinje Fibers/*physiology ; Tachycardia, Ventricular/*physiopathology/surgery ; Ventricular Dysfunction, Left/*physiopathology/surgery ; Young Adult

KIOM-79, a mixture of ethanol extracts from four herbs (parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix and Euphorbiae radix), has been developed for the potential therapeutic application to diabetic symptoms. Because screening of unexpected cardiac arrhythmia is compulsory for the new drug development, we investigated the effects of KIOM-79 on the action potential (AP) and various ion channel currents in cardiac myocytes. KIOM-79 decreased the upstroke velocity (Vmax) and plateau potential while slightly increased the duration of action potential (APD). Consistent with the decreased Vmax and plateau potential, the peak amplitude of Na+ current (INa) and Ca2+ current (ICa,L) were decreased by KIOM-79. KIOM-79 showed dual effects on hERG K+ current; increase of depolarization phase current (Idepol) and decreased tail current at repolarization phase (Itail). The increase of APD was suspected due to the decreased Itail. In computer simulation, the change of cardiac action potential could be well simulated based on the effects of KIOM-79 on various membrane currents. As a whole, the influence of KIOM-79 on cardiac ion channels are minor at concentrations effective for the diabetic models (0.1-10 microg/mL). The results suggest safety in terms of the risk of cardiac arrhythmia. Also, our study demonstrates the usefulness of the cardiac computer simulation in screening drug-induced long-QT syndrome.
Action Potentials/*drug effects ; Animals ; Cell Line ; Computer Simulation ; Female ; Ginger/chemistry ; Humans ; Ion Channels/*physiology ; Long QT Syndrome/diagnosis ; Male ; Membrane Potentials/drug effects/physiology ; Myocytes, Cardiac/*drug effects/physiology ; Patch-Clamp Techniques ; Plant Extracts/*pharmacology ; Pueraria/chemistry ; Purkinje Fibers/drug effects/physiology ; Rabbits ; Rats ; Rats, Sprague-Dawley

KIOM-79, a mixture of ethanol extracts from four herbs (parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix and Euphorbiae radix), has been developed for the potential therapeutic application to diabetic symptoms. Because screening of unexpected cardiac arrhythmia is compulsory for the new drug development, we investigated the effects of KIOM-79 on the action potential (AP) and various ion channel currents in cardiac myocytes. KIOM-79 decreased the upstroke velocity (Vmax) and plateau potential while slightly increased the duration of action potential (APD). Consistent with the decreased Vmax and plateau potential, the peak amplitude of Na+ current (INa) and Ca2+ current (ICa,L) were decreased by KIOM-79. KIOM-79 showed dual effects on hERG K+ current; increase of depolarization phase current (Idepol) and decreased tail current at repolarization phase (Itail). The increase of APD was suspected due to the decreased Itail. In computer simulation, the change of cardiac action potential could be well simulated based on the effects of KIOM-79 on various membrane currents. As a whole, the influence of KIOM-79 on cardiac ion channels are minor at concentrations effective for the diabetic models (0.1-10 microg/mL). The results suggest safety in terms of the risk of cardiac arrhythmia. Also, our study demonstrates the usefulness of the cardiac computer simulation in screening drug-induced long-QT syndrome.
Action Potentials/*drug effects ; Animals ; Cell Line ; Computer Simulation ; Female ; Ginger/chemistry ; Humans ; Ion Channels/*physiology ; Long QT Syndrome/diagnosis ; Male ; Membrane Potentials/drug effects/physiology ; Myocytes, Cardiac/*drug effects/physiology ; Patch-Clamp Techniques ; Plant Extracts/*pharmacology ; Pueraria/chemistry ; Purkinje Fibers/drug effects/physiology ; Rabbits ; Rats ; Rats, Sprague-Dawley