Differential beta-adrenergic regulation and phenotypic modulation of voltage-gated calcium currents in rat aortic myocytes.
1. We studied the beta-adrenergic regulation of voltage-gated Ca2+ channel currents using the whole-cell patch-clamp technique (18-22 degrees C) in freshly isolated and in cultured (1-20 days) rat aortic vascular smooth muscle cells (VSMCs). These currents include a transient low-voltage-activated (LVA) current and two L-type-related high-voltage-activated currents (HVA1 and HVA2, respectively). 2. At 10 microM, the beta-adrenergic agonist, isoprenaline, increased the HVA2 current (65 +/- 30%, n = 10) but had no effect on LVA and HVA1 currents. This potentiation was dose dependent in the range 0.01-10 microM, developed with a slow time course and was mimicked by elevating intracellular cyclic AMP using the permeant analogue dibutyryl cyclic AMP (100 microM). 3. In the well-differentiated freshly isolated myocytes, only the HVA1 current was recorded. In cultured cells, a predominant frequency of occurrence of LVA and HVA1 currents was observed in modulated and differentiated myocytes, respectively. The occurrence of the HVA2 current was stable during culture but this current disappeared when the cells were confluent. It was retrieved when the confluent cells were dispersed and subcultured. 4. In conclusion, we present evidence for a differential beta-adrenergic regulation of three types of Ca2+ channel current in adult rat aortic VSMCs. The differential expression of these currents, associated with marked changes in cell phenotypes in vitro, suggests that they serve distinct physiological functions.
Neveu
D
D
Centre de Recherches de Biochimie Macromoléculaire, CNRS, UPR 9008, INSERM U 249, Montpellier, France.
Quignard
J F
JF
Fernandez
A
A
Richard
S
S
Nargeot
J
J
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002453:Cell Cycle; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D015640:Ion Channel Gating; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D015220:Calcium Channels; D011943:Receptors, Adrenergic, beta; D003994:Bucladesine; D004247:DNA; D007545:Isoproterenol