An analogue of cAMP mimics developmental change in neonatal rat ventricular myocyte sodium current kinetics.
During development, the voltage dependence of single rat ventricular sodium channels shifts to more negative potentials. This shift is mimicked by coculture of neonatal myocytes with sympathetic neurons or by a 96-h exposure to 8-(4-chlorophenylthio) adenosine 3',5'-cyclic monophosphate (CPT-cAMP). The prolonged exposure to CPT-cAMP suggests that this is not a short-term modulatory effect on the sodium channel, but rather may reflect a trophic action. Here we examine the effect of CPT-cAMP using whole cell recording to investigate further the time period required for the effect. Sodium current was measured in a 50 mM NaCl bath solution at 20 +/- 1 degree C using the whole cell patch-clamp technique after exposure of myocytes to CPT-cAMP (0.25 mM) for 0,0.5,20, or 24 h. The relationship between the time constant of decay (tauh) of the sodium current and test voltage (V1) showed a shift to more hyperpolarizing voltages after exposure to CPT-cAMP for 24 h. In addition, the midpoint of the steady-state inactivation curve (V 1/2) was shifted from -75.8 +/- 1.1 mV (0-h exposure) to -83.3 +/- 1.6 mV (24-h exposure) (P < 0.05). Exposure for 0.5 h to CPT-cAMP did not alter the tauh or V 1/2 of the sodium current. However, exposure to CPT-cAMP for 20 h, followed by a 4-h washout period, produced an effect similar to that of the 24-h exposure. Thus the lack of effect of acute (0.5 h) exposure to CPT-cAMP and the persistence of the effect after washout of CPT-cAMP for 4 h suggest that adenosine 3',5'-cyclic monophosphate may play a trophic role in sodium channel development.
Lipka
L J
LJ
Department of Cardiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Siegelbaum
S A
SA
Robinson
R B
RB
Berman
M F
MF
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004553:Electric Conductivity; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D009206:Myocardium / Q000166:cytology; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors; D016276:Ventricular Function / Q000187:drug effects*
D015222:Sodium Channels; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000242:Cyclic AMP