Action potential prolongation and potassium currents in left-ventricular myocytes isolated from hypertrophied rabbit hearts.
We have studied the action potential characteristics and potassium currents in single left ventricular myocytes isolated from control and hypertrophied rabbit hearts. Left-ventricular hypertrophy (LVH) was induced following perinephritis-induced hypertension. Control animals underwent a sham operation. Animals were killed at 10 weeks post-operation. Left-ventricular myocytes were isolated by an enzyme dissociation technique. Action potential duration (APD) at 50 and 90% repolarisation was prolonged in myocytes obtained from hypertrophied compared to control hearts over the range of stimulation frequencies (0.1-1.5 Hz). This prolongation in APD was more pronounced in epicardial compared to endocardial myocytes. Steady-state ionic current, measured at the end of voltage clamp steps of 3-s duration, stepping at intervals of 10 mV, from a holding potential of -40 mV, was similar in control and hypertrophied myocytes. However, when normalised for capacitative cell surface area, steady-state current was significantly smaller in hypertrophied myocytes over the voltage range -40 to -60 mV and at potentials greater than +10 mV. Inward rectifier potassium current (IKl), identified as the barium chloride (0.1 mM)-sensitive current, contributed to the steady state current at negative potentials. Normalised IKl was significantly smaller in hypertrophied compared to control myocytes at potentials negative to -60 mV. Peak transient outward potassium current (Ito) density was reduced in hypertrophied compared to control myocytes at 0 and +10 mV, from a holding potential -80 mV (12.9 +/- 2.3 v 24.9 +/- 3.9 microA cm2, at +10 mV, P < 0.05). Steady-state inactivation of Ito was similar in control and hypertrophied myocytes. In conclusion, LVH induced by perinephritis hypertension in the rabbit is associated with a prolongation in APD. Reductions in IKl, sustained outward current and Ito may contribute to the prolongation in APD.
McIntosh
M A
MA
Department of Medical Cardiology, Royal Infirmary, Glasgow University, UK.
Cobbe
S M
SM
Kane
K A
KA
Rankin
A C
AC
D000200:Action Potentials; D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D019256:Cadmium Chloride / Q000494:pharmacology; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D004195:Disease Models, Animal; D004699:Endocardium / Q000166:cytology / Q000502:physiology*; D006973:Hypertension; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology*; D008297:Male; D018408:Patch-Clamp Techniques; D010496:Pericardium / Q000166:cytology / Q000502:physiology*; D010501:Perinephritis; D010627:Phenethylamines / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology; D016276:Ventricular Function
D017609:Barium Compounds; D002712:Chlorides; D010627:Phenethylamines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013449:Sulfonamides; C024986:barium chloride; D019256:Cadmium Chloride; C063533:dofetilide