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Ventricular Action Potential (ventricular + action_potential)
Selected AbstractsRole of Ca2+ -Activated Cl, Current in Ventricular Action Potentials of Sheep During Adrenoceptor StimulationEXPERIMENTAL PHYSIOLOGY, Issue 2 2001Arie O. Verkerk Adrenoceptor stimulation enhances repolarising and depolarising membrane currents to different extents in cardiac myocytes. We investigated the opposing effects of the repolarising Ca2+ -activated Cl, current (ICl(Ca)) and depolarising L-type Ca2+ current (ICa,L) on the action potential configuration of sheep ventricular myocytes stimulated with noradrenaline. Whole-cell current-clamp recordings revealed that noradrenaline accelerated and prolonged phase-1 repolarisation. We define the minimal potential at the end of phase-1 repolarisation as ,notch level'. Noradrenaline (1 ,M) caused the notch level to fall from 14 ± 2.6 to 7.8 ± 2.8 mV (n= 24), but left action potential duration, resting membrane potential or action potential amplitude unaffected. Whole-cell voltage-clamp recordings showed that 1 ,M noradrenaline increased both ICa,L and ICl(Ca), but it had no significant effect on the principal K+ currents. Blockage of ICl(Ca) by 0.5 mM 4,4,-diisothiocyanatostilbene-2,2,-disulphonic acid (DIDS) in both the absence and the presence of noradrenaline abolished phase-1 repolarisation. In the presence of noradrenaline, DIDS caused elevation of the plateau phase amplitude and an increase in the action potential duration. In conclusion, elevation of the plateau phase amplitude and action potential prolongation associated with an increased ICa,L upon adrenoceptor stimulation is prevented by an increased ICl(Ca) in sheep ventricular myocytes. [source] Abnormalities of the Repolarization Characteristics of Patients with Heart Failure Progress with Symptom SeverityANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2004Ch.B., Christopher C. E. Lang B.Sc. (Hons) Background:,Congestive heart failure is a common condition with high mortality. Many of these deaths are sudden and unexpected. Ventricular action potential, surface repolarization (QT interval), and dispersion of repolarization are prolonged in the failing heart, contributing to arrhythmogenesis and sudden death. We studied the relationship between QT and heart rate (RR interval) from ambulatory recordings using a novel method in patients with ischemic heart disease and varying degrees of left-ventricular impairment (IHD) and compared them to healthy subjects (HS). We compare the degree of abnormality with the functional impairment and ejection fraction. Methods:,Using a previously described automated method for continuous estimation of the QT/RR characteristic that incorporates a correction formula for compensation of QT adaptation lag (VERDA, Del Mar Reynolds Medical Ltd., Hertford, UK), we compared recordings from 41 IHD patients with age-matched HS. Results:,IHD Patients have prolonged 24-hour mean QTo (461 ms vs 426 ms, P < 0.01), and abnormal rate dependence relative to controls (24-hour mean slope: 0.20 vs 0.14, P < 0.001; J: 0.38 vs 0.28, P < 0.001). There is increased temporal variation in J with respect to HS. These abnormalities of repolarization increase with worsening NYHA class, but do not correlate with ejection fraction. Conclusions:,The use of a universal correction formula to compare dynamic QT data in IHD patients is inappropriate. The observed progressive abnormalities may be responsible for the high incidence of sudden death through promotion of arrhythmias. [source] Chronic effects of type 2 diabetes mellitus on cardiac muscle contraction in the Goto-Kakizaki ratEXPERIMENTAL PHYSIOLOGY, Issue 6 2007F. C. Howarth Type 2 diabetes mellitus accounts for more than 90% of all cases of diabetes mellitus, and cardiovascular complications are the major cause of mortality and death in diabetic patients. The chronic effects of type 2 diabetes mellitus on heart function have been investigated in the Goto-Kakizaki (GK) rat. Experiments were performed in GK rats and age-matched Wistar control rats at 18 months of age. The progressive effects of diabetes on glucose metabolism were monitored periodically by application of the glucose tolerance test. Ventricular action potentials were measured in isolated, perfused heart. Shortening and intracellular Ca2+ were measured in electrically stimulated ventricular myocytes. The GK rats displayed mild fasting hyperglycaemia and progressively worsening glucose tolerance. At 18 months of age and 180 min after intraperitoneal injection of glucose (2 g (kg body weight),1), blood glucose was 436 ± 47 mg dl,1 in GK rats compared with 153 ± 18 mg dl,1 in control animals. Heart weight to body weight ratio was significantly increased in GK rats (4.10 ± 0.09 mg g,1, n= 5) compared with control animals (3.36 ± 0.22 mg g,1, n= 4). Spontaneous heart rate was slightly reduced in GK rats compared with control rats. Although the amplitude of shortening was not altered, the amplitude of the Ca2+ transient was significantly increased in myocytes from GK rats (0.78 ± 0.11 ratio units) compared with control rats (0.50 ± 0.06 ratio units). Despite progressively worsening glucose metabolism, at 18 months of age the contractile function of the heart appears to be well preserved. [source] Inhibition of the formation or action of angiotensin II reverses attenuated K+ currents in type 1 and type 2 diabetesTHE JOURNAL OF PHYSIOLOGY, Issue 1 2001Yakhin Shimoni 1Transient and sustained calcium-independent outward K+ currents (It and ISS) as well as action potentials were recorded in cardiac ventricular myocytes isolated from two models of diabetes mellitus. 2Rats injected (i.v.) with streptozotocin (STZ, 100 mg kg,1) 6,10 days before cell isolation developed insulin-dependent (type 1) diabetes. It and ISS were attenuated and the action potential prolonged. Incubation of myocytes (6-9 h) with the angiotensin II (ATII) receptor blockers saralasin or valsartan (1 ,m) significantly augmented these currents. Inclusion of valsartan (1 g l,1) in the drinking water for 5,10 days prior to and following STZ injection partially prevented current attenuation. 3Incubation of myocytes from STZ-treated rats (6-9 h) with 1 ,m quinapril, an angiotensin-converting enzyme (ACE) inhibitor, significantly augmented It and ISS and shortened the ventricular action potential. It augmentation was not due to changes in steady-state inactivation or in recovery from inactivation. No acute effects of quinapril were observed. 4The effects of quinapril and valsartan were abolished by 2 ,m cycloheximide. 5Myocytes were isolated from the db/db mouse, a leptin receptor mutant that develops symptoms of non-insulin-dependent (type 2) diabetes. K+ currents in these cells were also attenuated, and the action potentials prolonged. Incubation of these cells (> 6 h) with valsartan (1 ,m) significantly enhanced the transient and sustained outward currents. 6These results confirm recent suggestions that cardiac myocytes contain a renin-angiotensin system, which is activated in diabetes. It is proposed that chronic release of ATII leads to changes in ionic currents and action potentials, which can be reversed by blocking the formation or action of ATII. This may underlie the proven benefits of ATII receptor blockade or ACE inhibition in diabetes, by providing protection against cardiac arrhythmias. [source] Familial And Acquired Long QT Syndrome And The Cardiac Rapid Delayed Rectifier Potassium CurrentCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2000Harry J Witchel SUMMARY 1. Long QT syndrome (LQTS) is a cardiac disorder characterized by syncope, seizures and sudden death; it can be congenital, idiopathic, or iatrogenic. 2. Long QT syndrome is so-named because of the connection observed between the distinctive polymorphic ventricular tachycardia torsade de pointes and prolongation of the QT interval of the electrocardiogram, reflecting abnormally slowed ventricular action potential (AP) repolarization. Acquired LQTS has many similar clinical features to congenital LQTS, but typically affects older individuals and is often associated with specific pharmacological agents. 3. A growing number of drugs associated with QT prolongation and its concomitant risks of arrhythmia and sudden death have been shown to block the ,rapid' cardiac delayed rectifier potassium current (IKr) or cloned channels encoded by the human ether-a-go-go -related gene (HERG; the gene believed to encode native IKr). Because IKr plays an important role in ventricular AP repolarization, its inhibition would be expected to result in prolongation of both the AP and QT interval of the electrocardiogram. 4. The drugs that produce acquired LQTS are structurally heterogeneous, including anti-arrhythmics, such as quinidine, non-sedating antihistamines, such as terfenadine, and psychiatric drugs, such as haloperidol. In addition to heterogeneity in their structure, the electrophysiological characteristics of HERG/IKr inhibition differ between agents. 5. Here, clinical observations are associated with cellular data to correlate acquired LQTS with the IKr/HERG potassium (K+) channel. One strategy for developing improved compounds in those drug classes that are currently associated with LQTS could be to design drug structures that preserve clinical efficacy but are modified to avoid pharmacological interactions with IKr. Until such time, awareness of the QT-prolongation risk of particular agents is important for the clinician. [source] Block of HERG-Carried K+ Currents by the New Repolarization Delaying Agent H 345/52JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2003Gregory J. Amos M.D. Ph.D. Introduction: The aim of this study was to analyze the block of HERG-carried membrane currents caused by H 345/52, a new antiarrhythmic compound with low proarrhythmic activity, in transfected mouse fibroblasts. Methods and Results: Using the whole-cell configuration of the voltage patch clamp technique, it was demonstrated that H 345/52 concentration-dependently blocked HERG-carried currents with an IC50 of 230 nM. H 345/52 preferentially bound to the open channel with unusually rapid kinetics and was trapped by channel closure. Voltage-independent behavior of H 345/52 was observed during both square-pulse and action potential clamp protocols. In contrast, the Class III agents dofetilide (10 nM) and almokalant (250 nM) demonstrated significant membrane potential-dependent effects during square-pulse clamp protocols. When using action potential clamp protocols, voltage dependence was seen with dofetilide but not with almokalant. Mathematical simulations of human ventricular action potentials predicted that the different voltage-dependent behaviors would not produce marked variations in action potential duration prolongation patterns. Conclusion: We propose that block of IKr is the principal mechanism by which H 345/52 delays repolarization in human myocardium. The voltage independence of HERG/IKr block is unlikely to underlie the low proarrhythmic potential, and ancillary effects on other membrane currents must be considered. (J Cardiovasc Electrophysiol, Vol. 14, pp. 651-658, June 2003) [source] | |||||||||||||