Adaptative modifications of right coronary myocytes voltage-gated K+ currents in rat with hypoxic pulmonary hypertension.
Chronic hypoxia (CH)-induced pulmonary hypertension (PHT) is well known to alter K+ channels in pulmonary myocytes. PHT induces right ventricle hypertrophy that increases oxygen demand; however, coronary blood flow and K+ channel adaptations of coronary myocytes during PHT remain unknown. We determined whether CH and PHT altered K+ currents and coronary reactivity and what impact they might have on right myocardial perfusion. Right ventricle perfusion, as attested by microspheres, was redistributed toward hypertrophied right ventricle [RV/LV (%)=0.59+/-0.07% in CH rats vs. 0.29+/-0.03 in control rats, P<0.05]. Whole-cell patch clamping showed a reduction of global outward current in hypoxic right coronary artery myocytes (H-RCA), whereas hypoxic left coronary artery myocytes exhibited an increase. K+ channel blockers revealed that a 4-aminopyridine (4AP)-sensitive current (Kv current) was decreased in H-RCA (14.3+/-1.1 vs. 23.4+/-2.5 pA/pF at 60 mV in control RCA, P<0.05) and increased in hypoxic left coronary artery myocytes (H-LCA; 26.4+/-3.8 vs. 11.8+/-1.6 pA/pF at 60 mV in control LCA, P<0.05). Constriction to 4AP was decreased in H-RCA when compared to normoxic control and increased in H-LCA when compared to LCA. Finally, we observed that the expression of Kv1.2 and Kv1.5 were lower in H-RCA than that in H-LCA. This study reveals that CH differentially regulates Kv channels in coronary myocytes. Hypoxia decreases Kv currents and therefore reduces vasoreactivity that contributes to an adaptative response leading to right hypertrophied ventricle perfusion enhancement at rest.
Hyvelin
Jean-Marc
JM
Laboratoire de Physiopathologie de la Paroi Artérielle, EA 3852, IFR 135, UFR Médecine, Université François Rabelais, 10 Bld Tonnellé, BP 3223, 37032, Tours Cedex, France. hyvelin@med.univ-tours.fr
Gautier
Mathieu
M
Lemaire
Marie-Christine
MC
Bonnet
Pierre
P
Eder
Véronique
V
D015761:4-Aminopyridine / Q000378:metabolism; D000818:Animals; D003331:Coronary Vessels / Q000166:cytology* / Q000473:pathology; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism*; D000860:Hypoxia / Q000150:complications / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D051381:Rats
D010455:Peptides; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; C064719:iberiotoxin; D015761:4-Aminopyridine