PMID- 18633640 OWN - NLM STAT- MEDLINE DCOM- 20090505 LR - 20211020 IS - 0031-6768 (Print) IS - 0031-6768 (Linking) VI - 457 IP - 4 DP - 2009 Feb TI - Adaptative modifications of right coronary myocytes voltage-gated K+ currents in rat with hypoxic pulmonary hypertension. PG - 721-30 LID - 10.1007/s00424-008-0546-x [doi] AB - 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. FAU - Hyvelin, Jean-Marc AU - Hyvelin JM AD - Laboratoire de Physiopathologie de la Paroi Arterielle, EA 3852, IFR 135, UFR Medecine, Universite Francois Rabelais, 10 Bld Tonnelle, BP 3223, 37032, Tours Cedex, France. hyvelin@med.univ-tours.fr FAU - Gautier, Mathieu AU - Gautier M FAU - Lemaire, Marie-Christine AU - Lemaire MC FAU - Bonnet, Pierre AU - Bonnet P FAU - Eder, Veronique AU - Eder V LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080717 PL - Germany TA - Pflugers Arch JT - Pflugers Archiv : European journal of physiology JID - 0154720 RN - 0 (Peptides) RN - 0 (Potassium Channel Blockers) RN - 0 (Potassium Channels, Voltage-Gated) RN - 773HER9B6T (iberiotoxin) RN - BH3B64OKL9 (4-Aminopyridine) SB - IM MH - 4-Aminopyridine/metabolism MH - Animals MH - Coronary Vessels/*cytology/pathology MH - Hypertension, Pulmonary/etiology/*metabolism MH - Hypoxia/complications/*metabolism MH - Male MH - Membrane Potentials/physiology MH - Muscle Contraction/physiology MH - Myocytes, Cardiac/cytology/*metabolism MH - Myocytes, Smooth Muscle/physiology MH - Patch-Clamp Techniques MH - Peptides/metabolism MH - Potassium Channel Blockers/metabolism MH - Potassium Channels, Voltage-Gated/*metabolism MH - Rats EDAT- 2008/07/18 09:00 MHDA- 2009/05/06 09:00 CRDT- 2008/07/18 09:00 PHST- 2007/11/19 00:00 [received] PHST- 2008/06/13 00:00 [accepted] PHST- 2008/07/18 09:00 [pubmed] PHST- 2009/05/06 09:00 [medline] PHST- 2008/07/18 09:00 [entrez] AID - 10.1007/s00424-008-0546-x [doi] PST - ppublish SO - Pflugers Arch. 2009 Feb;457(4):721-30. doi: 10.1007/s00424-008-0546-x. Epub 2008 Jul 17.