An analog of camp mimics developmental change in neonatal rat
ventricular myocyte sodium current kinetics.
Lipka, Leslie J., Steven A. Siegelbaum, Richard B. Robinson, and
Mitchell F. Berman.
Departments of Cardiology (L.J.L.), Pharmacology (L.J.L., R.B.R.,
S.A.S), Anesthesiology (M.F.B.), and the Center for Neurobiology and
Behavior and Howard Hughes Medical Institute (S.A.S.), Columbia
University College of Physicians & Surgeons, New York, New York
10032
APStracts 2:0384H, 1995.
During development, the voltage-dependence of single rat ventricular
sodium channels shifts to more negative potentials. This shift is
mimicked by co-culture of neonatal myocytes with sympathetic neurons
or by 96 hour exposure to 8-(4-chlorophenylthio)-adenosine 3':5'
-cyclic monophosphate (8-CPT-cAMP). The prolonged exposure to 8-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 8-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
degrees C using the whole-cell patch-clamp technique after exposure
of myocytes to 8-CPT-cAMP (0.25 mmol/L) for 0, 0.5, 20, or 24 hours.
The relationship between the time constant of decay (th) of the
sodium current and test voltage (Vt), showed a shift to more
hyperpolarizing voltages after exposure to 8-CPT-cAMP for 24 hours.
In addition, the midpoint of the steady-state inactivation curve
(V1/2) was shifted from -75.8 +/- 1.1 (0 hour exposure) to -83.3 +/
-?1.6 mV (24 hour exposure; p<0.05). 0.5 hour exposure to 8-CPT
-cAMP did not alter the th or V1/2 of the sodium current. However,
exposure to 8-CPT-cAMP for 20 hours, followed by a 4 hour washout
period, produced an effect similar to that of the 24 hour exposure.
Thus, the lack of effect of acute (0.5 hour) exposure to 8-CPT-cAMP
and the persistence of the effect after washout of 8-CPT-cAMP for
four hours suggest that cAMP may play a trophic role in sodium
channel development.
Received 16 August 1994; accepted in final form 12 June 1995.
APS Manuscript Number H740-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.