Expression of heart K+ channels in adrenalectomized and catecholamine-depleted reserpine-treated rats.
We studied cardiac outward K currents (transient and sustained) by the whole-cell patch-clamp technique and the Kv4.2, Kv4.3, Kv1.4, Kv1.5, Kv1.2 and Kv2.1 expression of voltage-gated K channel by RT-PCR, in ventricular myocytes from two models of catecholamine-depleted adult rats. We induced endogenous catecholamine depletion by reserpine treatment and used adrenalectomized rats as a model of plasma catecholamine depletion. In reserpine-treated rats (97% decrease in endogenous norepinephrine content of the heart), the amplitude of the transient outward current was decreased by 48% and Kv4.2 and Kv4.3 mRNA levels were decreased by 57% and 34%, respectively. The amount of Kv1.5 mRNA tripled, with no change in sustained current density. This increase was not confirmed by immunostaining for the Kv1.5 protein. The amplitude of K currents and their corresponding mRNA levels returned to control values following recovery from reserpine treatment. In contrast, in adrenalectomized rats (98% decrease in plasma epinephrine concentration), we observed no change in the amplitude of outward K currents or in Kv mRNA levels. These results suggested a role for sympathetic innervation and endogenous norepinephrine in the regulation of transcription of cardiac outward K currents in physiological and pathological situations.
Bru-Mercier
Gilles
G
CNRS, UMR 8078 Remodelage tissulaire et fonctionnel, Hôpital Marie Lannelongue, 133, avenue de la Résistance, 92350 Le Plessis Robinson, France.
Deroubaix
Edith
E
Capuano
Véronique
V
Ruchon
Yann
Y
Rücker-Martin
Catherine
C
Coulombe
Alain
A
Renaud
Jean-François
JF
D000315:Adrenalectomy; D000818:Animals; D002395:Catecholamines / Q000097:blood / Q000502:physiology*; D002478:Cells, Cultured; D004553:Electric Conductivity; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006321:Heart / Q000502:physiology; D006352:Heart Ventricles / Q000737:chemistry; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000032:analysis; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002395:Catecholamines; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D012110:Reserpine; D009638:Norepinephrine