The Cardiac Pacemaker Current if

Pacemaker Current if. Since the hyperpolarization-activated current, if, was originally associated with the diastolic depolarization phase of action potential in the sinoatrial (SA) node in 1979, its central role in the generation and control of pacemaker activity has become increasingly clear through a series of experimental findings, some of which have substantially modified the pre-existing theories of cardiac pacemaking and its modulation by the autonomic transmitters. Thus, the pacemaker current of Purkinje fibers, formerly described as a deactivating pure potassium (K) current, was found to be in fact, like the nodal if, inward and activating on hyperpolarization. Furthermore, in SA node cells, as well as mediating rhythm acceleration induced by catecholamines, if was found to underlie the slowing effect of low acetylcholine (ACh) concentrations, in contrast with the generally accepted hypothesis that activation of a K conductance is the main process responsible for cardiac slowing. A final, atypical property of if recently demonstrated concerns the activating action exerted on if by intracellular cAMP. Unlike that on other voltage-gated, cAMP-modulated cardiac channels, this action is independent of phosphorylation and involves a direct binding of cAMP to if channels. (J Cardiovasc Electrophysiol, Vol. 3, pp. 334–344, August 1992)     

老年黄斑变性的视网膜色素上皮及其视功能的改变

目的：应用黄斑区密集点矩阵视野并结合眼底荧光血管造影电脑眼底图像分析老年黄斑变性视网膜色素上皮损害与ＤＭＭＭ的视野光敏感度的改变，找出改变的规律有评价其应用价值。方法：用Ｈｕｍｐｈｒｅｙ－６４０视野计自行设计ＤＭＭＭ检测ＡＭＤ干性组５１人６４只眼湿性且２３人２７只眼，用Ｚｅｉｓｓ公司生产的ＫＯＮＴＲＯＮＥＬＥＫＴＲＯＮＩＫ Ｉｎａｇｅ Ａｎａｌｙｓｉｓ Ｄｉｖｉｓｉｏｎ－计算机图像分析仪总丢失量显     

大型Tokamak装置中环向场超导线圈的传热研究

分析了HT-7U超导Tokamak核聚变装置中环向场超导线圈上的涡流损耗热产生的机理和迫流式超临界氦对流换热等过程，特别针对等离子体快速破裂时，极短时间内在环向场磁体中所产生的较大的涡流损耗而引起的焦耳热，对环向场线圈盒与超导磁体之间的热传递过程加以研究。本文采用国际上通用的有限元分析软件ANSYS5.7进行计算，计算所得的结果较为乐观。     

Accentuated antagonism by angiotensin II on guinea-pig cardiac L-type Ca-currents enhanced by β-adrenergic stimulation

 To examine mechanism(s) underlying the accentuated antagonism by angiotensin II (A-II) on twitch tension, we recorded L-type Ca²⁺ currents (I _Ca,L) using conventional patch-clamp techniques in single, guinea-pig, ventricular myocytes. I _Ca,L was recorded by a step-pulse protocol after eliminating K⁺ conductances (internal Cs⁺ plus tetraethylammonium chloride and K⁺-free extracellular solution). A-II (100 nM) did not affect basal I _Ca,L, but inhibited I _Ca,L that had been enhanced (approximately 200% of control) by (ISO, isoproterenol 100 nM). The inhibitory action of A-II was concentration dependent (concentration eliciting 50% inhibition 88±9 pM, n=41) and the ISO-enhanced component of I _Ca,L was completely blocked by A-II at concentrations above 10 nM. CV-11974 (500 nM), an A-II type-1 receptor (AT₁) antagonist, prevented the inhibitory action of A-II. Pre-incubation with pertussis toxin (PTX) abolished the inhibitory effect of A-II. A-II also inhibited the I _Ca,L enhanced by histamine (500 nM) and forskolin (1 μM), but failed to affect I _Ca,L enhanced by intracellular cyclic adenosine monophosphate (1 mM). The inhibitory action of A-II may therefore involve AT₁ receptors/PTX-sensitive, guanine nucleotide-binding (G) proteins (Gi)/adenylate cyclase and partially explains the A-II-dependent accentuated antagonism of inotropy.     

Implantation of Active Can Implantable Defibrillators in the right Pectoral Region

Routinely the active can ICD is placed in the left side pectoral position, which theoretically gives optimal conditions for a low defibrillation threshold. Some patients, bowever, demand a right pectoral position, which possibly could result in a bigger defibrillation threshold. A right pectoral position was used in 3 of 85 active can ICDs implanted in our institution from 1994. the DFT was 12 J in two and 18 f in one patient. Thus, right pectoral implantation is feasible and offers an alternative approach in selected patients.     

导管射频消融治疗房室结折返性心动过速前后心率变异的改变

对２０例房室结折返性心动过速患者在射频消融前后进行心率变异频域和时域分析，以了解射频消融对心脏自主神经系统的影响。结果显示，心率变异的极低频段（ＵＬＦＰ）、低频段（ＬＦＰ）、高频段（ＨＦＰ）及总能谱（ＴＦＰ）均较射频消融前降低（Ｐ〈０．０５）。提示射频消融对心脏交感神经、融交感神经均有损害，而以副交感神经损害为主。     

On the mechanism of increased potassium conductance by the potassium channel opener BRL 34915 in Isolated ventricular myocytes

The potassium conductance increased by BRL 34915 (BRL, cromakalim) was studied in single guinea pig ventricular myocytes by using a whole cell voltage-clamp technique. In control voltage-clamp recordings, the late current-voltage relation showed a distinct inward rectification. BRL (1–100 μM) shortened the action potential and diminished or abolished inward rectification but had no effect on the slope conductance and currents flowing during hyperpolarizing clamp steps. BRL did not decrease the slow inward current but accelerated the time constant of activation and amplitude of the outward current. Cd markedly decreased (0.2 mM) or abolished (0.4–0.6 mM) the slow inward current and BRL induced a faster outward shift of late current to a greater value. Glybenclamide (10 μM), a blocker of ATP-sensitive K⁺ channels, had little effect of its own on action potential, membrane currents, and I-V relation. However, in the presence of BRL, glybenclamide abolished BRL effects on action potential and currents and restored inward rectification. It is concluded that the mechanism by which BRL shortens the action potential is a faster growth of an outward current due to the reduction or abolition of the inward rectification of an ATP-dependent potassium channel. The reduction in force in non-isolated tissues appears to be an indirect result of the action potential shortening and not of a decreased slow inward current.     

EFFECTS OF STROPHANTHIDIN ON THE SLOW INWARD CURRENT IN GUINEA-PIG ISOLATED VENTRICULAR MYOCYTES

1. The effect of strophanthidin on the slow inward current (Isi) and on contractile force were studied in guinea-pig isolated ventricular myocytes and intact papillary muscles, respectively. In myocytes, both low (10 nmol/L) and high (1-10 mumols/L) concentrations had small or no effects in either direction on Isi whereas norepinephrine (10-100 nmol/L) increased it. To determine whether the same results are obtained after decreasing or increasing intracellular calcium or sodium, the same concentrations of strophanthidin were tested in different procedures that are known to (i) increase [Ca]i and decrease [Na]i (high [Ca]o, 3.6-5.4 mmol/L; low [Na]o, 112 mmol/L; (ii) decrease [Ca]i and increase [Na]i (low [Ca]o, 0.45-1 mmol/L; Sr, 1 mmol/L; (iii) decrease [Ca]i and [Na]i (Cd, 0.1-0.2 mmol/L); and (iv) increase [Ca]i and [Na]i (veratridine, 0.2 mumol/L). High [Ca]o and veratridine increased whereas low [Ca]o and Cd decreased Isi. In contrast, during these various procedures, strophanthidin had small and inconsistent effects at a low or high concentration. In intact papillary muscles, low strophanthidin decreased whereas high strophanthidin increased contractile force. It is concluded that strophanthidin has little direct or indirect effect on Isi and that the decrease in force by low and increase in force by high concentrations in intact muscle are probably related to demonstrated decrease and increase, respectively, in intracellular sodium activity.     

Frontal versus transcorneal stimulation to induce maximal electroshock seizures or kindling in mice and rats

Frontal stimulation, i.e. electrical stimulation where electrodes are pressed on the skin of the intact frontal skull of mice or rats, may represent a more humane alternative to the widely used transcorneal stimulation to induce electroshock seizures. The aim of this work was to directly compare transcorneal and frontal stimulation in eliciting maximal electroshock-induced seizures (MES) in mice and the anticonvulsant effect of carbamazepine (CBZ) and phenytoin (PHT) on thus produced seizures. In addition, we stimulated mice and rats repeatedly via transcorneal and frontal electrodes to see whether kindling is produced by this procedure. Two electroshock tests were used in mice, i.e. maximal electroshock seizure threshold (MEST) test and MES generated by supramaximal stimulation (50 mA). Frontal stimulation resulted in lower convulsive threshold than in the case of corneal stimulation. Both CBZ and PHT produced dose-dependent increases in seizure threshold for both sites of stimulation, i.e. transcorneal and frontal. As regards type of electrodes, higher doses of PHT were required to increase seizure threshold in the case of frontal than transcorneal stimulation. Supramaximal stimulation (50 mA) yielded comparable ED₅₀ values regardless of the site of stimulation. Furthermore, once-daily stimulation of mice, regardless of the placement of electrodes, did not induce any changes in convulsive threshold. We also attempted to kindle mice and rats via corneal and frontal electrodes by repetitive electrical stimulation using currents which initially did not produce generalized clonic seizures. Mice were stimulated once daily for 2 s with 3 mA (corneal electrodes) or 2 mA (frontal electrodes) and rats were stimulated twice daily for 4 s at 8 mA (corneal electrodes) or 5 mA (frontal electrodes). With corneal stimulation in rats there was a clear progression of kindling development which was not the same in nature when compared with corneally-stimulated mice. Frontal stimulation did not produce kindling. Moreover, corneal stimulation was better tolerated by rats, while in mice high mortality was seen after either method of current delivery. Our data indicate that frontal electrodes can be used as an alternative to transcorneal stimulation to produce MES by supramaximal or threshold current intensities as screening procedures in antiepileptic drug (AED) development. Nevertheless, this type of stimulation cannot be used to produce minimal electroshock seizures and seems not to be useful to produce kindling in rats and mice.