title: An analogue of cAMP mimics developmental change in neonatal rat ventricular myocyte sodium current kinetics.
abstract: 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.
authors.affiliation: Department of Cardiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Lipka
authors.forename: S A
authors.initials: SA
authors.lastname: Siegelbaum
authors.forename: R B
authors.initials: RB
authors.lastname: Robinson
authors.forename: M F
authors.initials: MF
authors.lastname: Berman
mesh_terms: 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*
chemical_list: D015222:Sodium Channels; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000242:Cyclic AMP