Differential effects ofd, l-Sotalol andd-Sotalol on isoproterenol-increased delayed rectifier outward potassium current in guinea pig single ventricular myocytes

1998 ◽  
Vol 18 (1) ◽  
pp. 13-17
Author(s):  
Yao Xiaozhou ◽  
Natalia C. Yannoulis ◽  
Johann Kiehn ◽  
Lu Zaiying ◽  
Zhao Huayue ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Potassium Current ◽  
Ventricular Myocytes ◽  
Delayed Rectifier ◽  
Differential Effects ◽  
Single Ventricular Myocytes ◽  
Outward Potassium Current

Ionic Mechanisms Mediating the Differential Effects of Methohexital and Thiopental on Action Potential Duration in Guinea Pig and Rabbit Isolated Ventricular Myocytes 

1999 ◽  
Vol 90 (1) ◽  
pp. 156-164 ◽  
Author(s):  
Anatoly E. Martynyuk ◽  
Timothy E. Morey ◽  
Pekka M.J. Raatikainen ◽  
Christoph N. Seubert ◽  
Donn M. Dennis
Keyword(s):  
Guinea Pig ◽  
Potassium Current ◽  
Ventricular Myocytes ◽  
Inward Rectifier ◽  
Delayed Rectifier ◽  
Delayed Rectifier Potassium Current ◽  
Ionic Mechanisms ◽  
Inward Rectifier Potassium Current ◽  
Calcium Inward Current ◽  
Outward Potassium Current

Background Commonly used barbiturate anesthetics may significantly influence cardiac electrophysiologic characteristics. The authors evaluated thiopental (a thiobarbiturate) and methohexital (an oxybarbiturate), two compounds with similar physicochemical properties but different structures, to determine whether they have distinct effects on the major ionic currents that determine action potential duration (APD) in ventricular myocytes. Methods The effects of thiopental and methohexital (50 microM) on APD at 50% (APD50) and 90% (APD90) repolarization were studied in guinea pig and rabbit single ventricular myocytes using the patch-clamp technique in a whole-cell configuration. The ionic mechanisms underlying the APD changes were evaluated by measuring the anesthetics' effects on the L-type calcium inward current, the inward rectifier potassium current, and the delayed rectifier potassium current in guinea pig cells and on the transient outward potassium current in rabbit cells. Results Thiopental and methohexital caused opposite effects on APD. Whereas thiopental prolonged APD50 and APD90 in guinea pig and rabbit ventricular myocytes, methohexital shortened them. Thiopental markedly depressed both the inward and outward components of the inward rectifier potassium current, whereas methohexital caused minimal inhibition of the inward component and no change in the outward component. The delayed rectifier potassium current was inhibited by thiopental but significantly potentiated by methohexital. Neither thiopental nor methohexital significantly affected the transient outward potassium current or the L-type calcium inward current. Conclusions Despite their similar lipid solubilities, molecular weights, and pKa values, thiopental increased and methohexital decreased the APD in ventricular myocytes by predominantly inhibiting the inward rectifier potassium current and the delayed rectifier potassium current and by increasing the delayed rectifier potassium current, respectively. These characteristics suggest distinct structure-specific actions of barbiturates on the function of myocardial ionic channels.

scholarly journals Cell swelling has differential effects on the rapid and slow components of delayed rectifier potassium current in guinea pig cardiac myocytes.

1995 ◽  
Vol 106 (6) ◽  
pp. 1151-1170 ◽  
Author(s):  
S A Rees ◽  
J I Vandenberg ◽  
A R Wright ◽  
A Yoshida ◽  
T Powell
Keyword(s):  
Guinea Pig ◽  
Potassium Current ◽  
Mean Value ◽  
Cell Swelling ◽  
Delayed Rectifier ◽  
Patch Clamp Technique ◽  
Differential Effects ◽  
Delayed Rectifier Current ◽  
Delayed Rectifier Potassium Current ◽  
Ionic Conductances

Cell swelling has been shown to cause activation of a variety of cardiac sarcolemmal ionic conductances including potassium channels. The aim of this study was to investigate the effect of swelling on the two subtypes of delayed rectifier potassium current (IKr and IKs) in single guinea pig myocytes using the whole-cell configuration of the patch clamp technique. When the holding potential was set at -40 mV and stepped to +40 mV for 1 s under isoosmotic conditions (300 mOsm) a delayed rectifier current (IK) was activated (0.86 +/- 0.05 nA; n = 43). Switching to a hypoosmotic solution (200 mOsm) caused a rapid increase in IK to a mean value of 1.43 +/- 0.10 nA (p < 0.05; n = 43). The effect of swelling on the two subtypes of IK was studied by analysis of deactivating tail currents using an envelope of tails protocol (stepping from -40 to +40 mV for 18 different pulse durations between 50 ms and 2.9 s; n = 16). Swelling caused a decrease in current amplitude measured at the end of the pulse (and IKtail) at short durations (< or = 150 ms) however, when the pulse duration was > 1 s swelling caused a significant increase in current. Using a pulse protocol to measure IKr with minimal contamination by IKs (voltage step from -40 to -10 mV for 250 ms) a 50-100 pA current was elicited which could be completely blocked by dofetilide (0.2 microM; n = 3). Introduction of hypoosmotic solution caused a significant decrease in IKr and when dofetilide (0.2 or 1.0 microM) was introduced the current remaining was decreased further (p < 0.05; n = 5), but was not completely blocked, thus suggesting that swelling had decreased the ability of dofetilide to block IKr. Similar results were obtained over a range of dofetilide concentrations and with a second IKr blocker, La3+. In Ca(2+)-free external solutions, pulsing to -10 mV for 500 ms to measure IKr in the absence of IKs, and to +60 mV for 5 s (with 0.2 microM dofetilide) to evoke only IKs, it was clear that swelling significantly increased IKs (pulse and tail currents) and decreased IKr. In addition, when measured using the perforated patch method, swelling modulated IKt and IKs in a similar fashion. We conclude that swelling has differential effects on the subtypes of the classical cardiac IK, which may have important implications in our understanding of the mechanisms underlying ischaemia- and reperfusion-induced arrhythmogenesis.

Endothelin enhances delayed potassium current via phospholipase C in guinea pig ventricular myocytes

1992 ◽  
Vol 262 (2) ◽  
pp. H345-H354 ◽  
Author(s):  
Y. Habuchi ◽  
H. Tanaka ◽  
T. Furukawa ◽  
Y. Tsujimura ◽  
H. Takahashi ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Phospholipase C ◽  
Potassium Current ◽  
Ventricular Myocytes ◽  
Delayed Rectifier ◽  
Internal Solution ◽  
Kinase C ◽  
K Current ◽  
20 Nm ◽  
Pkc Activation

The effects of endothelin, a novel vasoconstrictive peptide, on the delayed rectifier K+ current (IK) were examined in single dialyzed cells from guinea pig ventricles. Either big endothelin or endothelin-1 enhanced IK at a dissociation constant of 2 nM with L-type Ca2+ current being unaffected. Under intracellular perfusion with pCa 7.6 solution, 3 nM big endothelin increased IK by 55 +/- 38.5%. Either pretreatment with 10 microM 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H 7) or a low Ca2+ [10 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) and minus CaCl2] internal solution diminished the enhancement. Preceding stimulation of protein kinase C (PKC) by 10-20 nM 12-O-tetradecanoylphorbol-13-acetate also reduced the degree of enhancement. When Na+ was eliminated from the solutions, endothelin increased IK distinctively in cells internally dialyzed with a low Ca2+ solution. This enhancement was not abolished by either pretreatment with H 7 or by removal of Ca2+ from the external perfusate but by increasing the internal EGTA concentration to 40 mM. Preincubation with ryanodine or internal perfusion with heparin also reduced the IK enhancement under Na(+)-free conditions. Intracellular application of 200 microM guanosine 5'-O-(3-thiotriphosphate) effectively attenuated the effect of endothelin. It is concluded that endothelin enhances IK via phospholipase C-mediated PKC activation and intracellular Ca2+ mobilization. GTP-binding protein is involved in these reactions.

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