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Selected Publication:
Kockskämper, J; Sendhoff, K; Erlenkamp, S; Bordusa, F; Cerovsky, V; Glitsch, HG.
Differences in the protein-kinase-A-dependent regulation of CFTR Cl- channels and Na+-K+ pumps in guinea-pig ventricular myocytes.
Pflugers Arch. 2001; 441(6):807-815
Doi: 10.1007/s004240000485
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- Leading authors Med Uni Graz
- Kockskämper Jens
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- Abstract:
- Protein-kinase-A- (PKA-) dependent regulation of cystic fibrosis transmembrane conductance regulator (CFTR) Cl- current (I(CFTR)) and Na+-K+ pump current (Ip) was studied in single guinea-pig ventricular myocytes. Both currents were measured simultaneously by means of whole-cell recording at 30 degrees C. The adenylyl cyclase activator forskolin was used to stimulate PKA activity. At -20 mV, forskolin (4 microM) induced a fast activation of I(CFTR) and a delayed stimulation of Ip. Despite the strikingly different time courses, however, the potency of the drug to regulate both currents was identical. Half-maximal activation of I(CFTR) and stimulation of Ip, respectively, were observed at 9.6 x 10(-8) M and 9.9 x 10(-8) M forskolin. Inclusion of a specific peptide inhibitor of PKA in the pipette solution (PKI, 20 microM) blocked forskolin's effect on Ip. However, regardless of the time allowed for cell dialysis, there still was a marked, transient activation of I(CFTR), which could be prevented by: (1) a short pre-activation of I(CFTR) with forskolin or (2) the additional inclusion in the pipette solution of a synthetic peptide (Ht31 peptide, 60 microM) that interferes with PKA binding to its anchoring proteins. Thus, there is a tight functional coupling between PKA and CFTR Cl- channels in guinea-pig ventricular myocytes. The coupling is probably due to the close physical proximity of channels and kinases mediated by PKA anchoring proteins. Na+-K+ pumps, on the other hand, though also regulated by PKA, appear to be loosely coupled to the kinases.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Chloride Channels - metabolism
- Cyclic AMP-Dependent Protein Kinases - metabolism
- Cystic Fibrosis Transmembrane Conductance Regulator - metabolism
- Dose-Response Relationship, Drug - metabolism
- Forskolin - pharmacology
- Guinea Pigs - pharmacology
- Heart Ventricles - cytology
- Membrane Potentials - drug effects
- Membrane Proteins - metabolism
- Muscle Fibers - cytology
- Myocardium - cytology
- Na(+)-K(+)-Exchanging ATPase - metabolism
- Patch-Clamp Techniques - metabolism
- Find related publications in this database (Keywords)
- AKAP
- CFTR
- Cl- channel
- Na+-K+ pump
- protein kinase A
- ventricular myocyte