The slow component of the delayed rectifier potassium current in undiseased human ventricular myocytes

Objective: The purpose of this study was to investigate the properties of the slow component of the delayed rectifier potassium current (I-Ks) in myocytes isolated from undiseased human left ventricles. Methods: The whole-cell configuration of the patch-clamp technique was applied in 58 left ventricular myocytes from 15 hearts at 37 degreesC. Nisoldipine (1 muM) was used to block inward calcium current (I-Ca) and E-4031 (1-5 muM) was applied to inhibit the rapid component of the delayed rectifier potassium current (I-Ks). Results: In 31 myocytes an E-4031 insensitive, but L-735,821 and chromanol 293B sensitive, tail current was identified which was attributed to the slow component of I-K (I-Ks). Activation of I-Ks was slow (tau = 903 +/- 101 ms at 50 mV, n = 24), but deactivation of the current was relatively rapid ( tau =122.4 +/- 11.7 ms at -40 mV, n = 19). The activation of I-Ks was voltage independent but its deactivation showed clear voltage dependence. The deactivation was faster at negative voltages (about 100 ms at -50 mV) and slower at depolarized potentials (about 300 ms at 0 mV). In six cells, the reversal potential was -81.6 +/- 2.8 mV on an average which is close to the K+ equilibrium potential suggesting K+ as the main charge carrier. Conclusion: In undiseased human ventricular myocytes, I-Ks exhibits slow activation and fast deactivation kinetics. Therefore, in humans I-Ks differs from that reported in guinea pig, and it best resembles I-Ks described in dog and rabbit ventricular myocytes

A UNITARY APPROACH TO SOME CLASSICAL INEQUALITIES

Abstract. In this paper, we will give a unitary approach to some classical inequalities. We will show that these results could be proved in the same manner

Association between varicose veins anatomical pattern and procedural complications following endovascular laser photothermolysis for chronic venous insufficiency

We sought to assess clinical characteristics and pattern of collateral network involvement associated with development of truncal (systematized) versus diffuse/non-truncal (non-systematized) varicose veins (VVs) in patients undergoing endovascular laser photothermolysis for chronic venous insufficiency (CVI). Secondly, we aimed to assess whether the type of VVs influenced the procedural complications of endovascular laser therapy. A total of 508 patients with hydrostatic VVs of the lower limbs who underwent endovenous laser treatment were included, out of which 84.1% (n=427) had truncal VVs (group 1) and 15.9% (n=81) had diffuse (non-systematized) VVs (group 2). Patients with truncal varices were significantly older (47.50±12.80 vs 43.15±11.75 years, P=0.004) and those with associated connective tissue disorders were more prone to present diffuse VVs (P=0.004). Patients in group 1 presented a significantly higher number of Cockett 1 (P=0.0017), Cockett 2 (P=0.0137), Sherman (P<0.0001), and Hunter (P=0.0011) perforator veins compared to group 2, who presented a higher incidence of Kosinski perforators (P<0.0001). There were no significant differences regarding postoperative complications: thrombophlebitis (P=0.773), local inflammation (P=0.471), pain (P=0.243), paresthesia (P=1.000), or burning sensation (P=0.632). Patients with more advanced CEAP (clinical, etiologic, anatomic, pathophysiologic) classes were older (P<0.0001), more were males (39.05 vs 27.77%, P=0.0084), more were prone to present ulcers (P<0.0001) and local hyperthermia (P=0.019), and presented for endovenous phlebectomy after a longer time from symptom onset. In patients with CVI, systematized VVs were associated with a more severe clinical status and a distinct anatomical pattern of perforators network compared to non-systematized VVs, which is more common in advanced stages

The cellular electrophysiologic effect of a new amiodarone like antiarrhythmic drug GYKI 16638 in undiseased human ventricular muscle: comparison with sotalol and mexiletine

The cellular electrophysiologic effect of GYKI 16638, a new antiarrhythmic compound was studied and compared with that of sotalol and mexiletine in undiseased human right ventricular muscle preparation by applying the conventional microelectrode technique. GYKI 16638 (5 muM), at stimulation cycle length of 1000 ms, lengthened action potential duration (APD(90)) from 338.9 +/- 28.6 ms to 385.4 +/- 24 ms (n = 9, p < 0.05). This APID lengthening effect, unlike that of sotalol (30 muM), was rate-independent. GYKI 16638, contrary to sotalol and like mexiletine (10 muM), exerted a use-dependent depression of the maximal rate of depolarization (V-max) which amounted to 36.4 +/- 11.7 % at cycle length of 400 ms (n = 5, p < 0.05) and was characterised with an offset kinetical time constant of 298.6 +/- 70.2 ms. It was concluded that GYKI 16638 in human ventricular muscle shows combined Class IB and Class III antiarrhythmic properties, resembling the electrophysiological manifestation seen after chronic amiodarone treatment

Effects of endothelin-1 on calcium and potassium currents in undiseased human ventricular myocytes

Endothelins have been reported to exert a wide range of electrophysiological effects in mammalian cardiac cells. These results are controversial and human data are not available. Our aim was to study the effects of endothelin-l (ET-1, 8 nmol/l) on the L-type calcium current (ICa-L) and various potassium currents (rapid component of the delayed rectifier, I-Kr; transient outward current, I-to; and the inward rectifier K current, I-K1) in isolated human ventricular cardiomyocytes. Cells were obtained from undiseased donor hearts using collagenase digestion via the segment perfusion technique. The whole-cell configuration of the patch-clamp technique was applied to measure ionic currents at 37 degreesC. ET-1 significantly decreased peak I-Ca,I-L from 10.2+/-0.6 to 6.8+/-0.8 pA/pF at +5 mV (66.7% of control, P <0.05, n=5). This reduction of peak current was accompanied by a lengthening of inactivation. The voltage dependence of steady-state activation and inactivation was not altered by ET-1. I-Kr, measured as tail current amplitudes at -40 mV, decreased from 0.31+/-0.02 to 0.06+/-0.02 pA/pF (20.3% of control, P <0.05, n=4) after exposure to ET-1. ET-I failed to change the peak amplitude of I-to, measured at +50 mV (9.3+/-4.6 and 9.0+/-4.4 pA/pF before and after ET-1, respectively), or steady-state I-K1 amplitude, measured at the end of a 400-ms hyperpolarization to -100 mV (3.6+/-1.4 and 3.7+/-1.4 pA/pF, n=4). The present results indicate that in undiseased human ventricular myocytes ET-1 inhibits both ICa-L and I-Kr; however, the degree of suppression of the two currents is different