Inhibition of voltage-dependent Na+ and K+ currents by forskolin in nodes of Ranvier |
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Authors: | Neil A Castle |
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Institution: | (1) Anesthesia Research Laboratories, Harvard Medical School, Brigham and Women's Hospital, 75 Francis Street, 02115 Boston, MA, USA |
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Abstract: | The effect of forskolin on voltage-activated Na+ and K+ currents in nodes of Ranvier from the toad, Bufo marinus, has been examined using the vaseline-gap voltageclamp technique. Peak Na+ currents (I
Na) were reduced by 35% and the rate of decline of Na+ current during continuous depolarization was accelerated following treatment with 450 M forskolin. However, the voltage-dependence of steady-state inactivation as well as the rate of recovery from fast inactivation remained unchanged. Upon repetitive depolarization at 1–10 Hz, a further inhibition of I
Na ( 60%) was observed. This use-dependent or phasic inhibition recovers slowly at -80 mV ( 13 s) and had a voltage-dependence like that of activation of the Na conductance. Near maximal steady-state phasic inhibition occurred with depolarizing pulse durations of only 4 ms, consistent with a direct involvement of the open Na+ channel in the blocking process. Inhibition of the delayed K+ current (I
K) was characterized by a concentration-dependent reduction in steady-state current amplitude (IC50 80 M) and a concentration-independent acceleration of current inactivation. A similar inhibition of I
K was obtained with 1,9-dideoxyforskolin, a homolog which does not activate adenylate cyclase (AC). The results suggest that the inhibition of I
K and perhaps I
Na follows directly from drug binding and is not a consequence of AC activation. |
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Keywords: | Nerve Na+ channel K+ channel Forskolin Node of Ranvier |
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