REGULATION OF THE BETA-STIMULATION OF THE NA-K+ PUMP CURRENT IN GUINEA-PIG VENTRICULAR MYOCYTES BY A CAMP-DEPENDENT PKA PATHWAY()

Citation
J. Gao et al., REGULATION OF THE BETA-STIMULATION OF THE NA-K+ PUMP CURRENT IN GUINEA-PIG VENTRICULAR MYOCYTES BY A CAMP-DEPENDENT PKA PATHWAY(), Journal of physiology, 477(3), 1994, pp. 373-380
Citations number
28
Categorie Soggetti
Physiology
Journal title
ISSN journal
00223751
Volume
477
Issue
3
Year of publication
1994
Pages
373 - 380
Database
ISI
SICI code
0022-3751(1994)477:3<373:ROTBOT>2.0.ZU;2-K
Abstract
1. The whole-cell patch-clamp technique was employed with the free int racellular [Ca2+] fixed at 1.4 mu m in order to study the isoprenaline (Iso)-induced increase in the Na+-K+ pump current (I-p) in acutely is olated guinea-pig ventricular myocytes. 2. The non-specific protein ki nase inhibitor, H-7, eliminated the stimulatory effect of Lso, suggest ing a phosphorylation step is involved in the beta-agonist stimulation of I-p. 3. H-7 or the phosphatase inhibitor calyculin A individually had no effect on basal I-p; however, when I-p was first increased by I so, H-7 inhibited and calyculin A further increased I-p. This suggests phosphorylation is not important to the basal regulation of I-p, but does have an effect during beta-stimulation. 4. The Iso-induced increa se in I-p could be mimicked by adding the membrane-permeant cAMP analo gue chlorophenylthio-cAMP, blocking cAMP degradation with IBMX or stim ulating cAMP production with forskolin. Alternatively the protein kina se A inhibitor PKI blocked the stimulatory effect of Iso. This suggest s the Iso-induced phosphorylation responsible for increasing I-p is me diated by cAMP, which then activates protein kinase A (PKA). 5. We con clude that the beta-agonist-induced increase in I-p in the presence of high intracellular [Ca2+ is mediated by a phosphorylation step via th e cAMP-dependent PKA pathway. During beta-stimulation, this increase i n active Na+-K+ transport can serve to offset the effects of increases in passive membrane conductances.