PMID- 2158748
OWN - NLM
STAT- MEDLINE
DCOM- 19900525
LR  - 20171213
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 258
IP  - 4 Pt 2
DP  - 1990 Apr
TI  - Inhibition of cardiac Na+ currents by isoproterenol.
PG  - H977-82
AB  - The mechanism by which the beta-adrenergic agonist isoproterenol (ISO) modulates 
      voltage-dependent cardiac Na+ currents (INa) was studied in single ventricular 
      myocytes of neonatal rat using the gigaseal patch-clamp technique. ISO inhibited 
      INa reversibly, making the effect readily distinguishable from the monotonic 
      decrease of INa caused by the shift in gating that customarily occurs during 
      whole cell patch-clamp experiments (E. Fenwick, A. Marty, and E. Neher, J. 
      Physiol. Lond. 331: 599-635, 1982; and J. M. Fernandez, A. P. Fox, and S. Krasne, 
      J. Physiol. Lond. 356: 565-585, 1984). The inhibition was biphasic, having fast 
      and slow components, and was voltage-dependent, being more pronounced at 
      depolarized potentials. In whole cell experiments the membrane-permeable 
      adenosine 3',5'-cyclic monophosphate (cAMP) congener 8-bromo-cAMP reduced INa. In 
      cell-free inside-out patches with ISO present in the pipette, guanosine 
      5'-triphosphate (GTP) applied to the inner side of the membrane patch inhibited 
      single Na+ channel activity. This inhibition could be partly reversed by 
      hyperpolarizing prepulses. The nonhydrolyzable GTP analogue 
      guanosine-5'-O-(3-thiotriphosphate) greatly reduced the probability of single Na+ 
      channel currents in a Mg2(+)-dependent manner. We propose that ISO inhibits 
      cardiac Na+ channels via the guanine nucleotide binding, signal-transducing G 
      protein that acts through both direct (membrane delimited) and indirect 
      (cytoplasmic) pathways.
FAU - Schubert, B
AU  - Schubert B
AD  - Department of Physiology and Molecular Biophysics, Baylor College of Medicine, 
      Houston, Texas 77030.
FAU - Vandongen, A M
AU  - Vandongen AM
FAU - Kirsch, G E
AU  - Kirsch GE
FAU - Brown, A M
AU  - Brown AM
LA  - eng
GR  - HL-36930/HL/NHLBI NIH HHS/United States
GR  - HL-37044/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Sodium Channels)
RN  - 0 (Thionucleotides)
RN  - 23583-48-4 (8-Bromo Cyclic Adenosine Monophosphate)
RN  - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate))
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - I38ZP9992A (Magnesium)
RN  - L628TT009W (Isoproterenol)
SB  - IM
MH  - 8-Bromo Cyclic Adenosine Monophosphate/pharmacology
MH  - Animals
MH  - Cells, Cultured
MH  - Electrophysiology/methods
MH  - Guanosine 5'-O-(3-Thiotriphosphate)
MH  - Guanosine Triphosphate/analogs & derivatives/pharmacology
MH  - Isoproterenol/*pharmacology
MH  - Magnesium/pharmacology
MH  - Myocardium/cytology/*metabolism
MH  - Sodium Channels/*drug effects/physiology
MH  - Thionucleotides/pharmacology
EDAT- 1990/04/01 00:00
MHDA- 1990/04/01 00:01
CRDT- 1990/04/01 00:00
PHST- 1990/04/01 00:00 [pubmed]
PHST- 1990/04/01 00:01 [medline]
PHST- 1990/04/01 00:00 [entrez]
AID - 10.1152/ajpheart.1990.258.4.H977 [doi]
PST - ppublish
SO  - Am J Physiol. 1990 Apr;258(4 Pt 2):H977-82. doi: 
      10.1152/ajpheart.1990.258.4.H977.