ATP regulates muscarine‐sensitive potassium current in dissociated bull‐frog primary afferent neurones.

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Abstract
1. Bull‐frog dorsal root ganglion cells in primary culture were voltage clamped in the whole‐cell configuration. The pipette solution contained ATP (5 mM). 2. Step depolarizations (5‐70 mV, 0.1‐1 s) from a holding potential close to the resting potential (range, ‐64 to ‐79 mV) evoked a non‐inactivating potassium current with properties indistinguishable from those which have been reported for the M‐current of bull‐frog sympathetic neurones. 3. An unhydrolysable ATP analogue APP(NH)P (5 mM), substitute with ATP in the pipette solution, did not support the M‐current activation. 4. Bath application of ATP (30 nM‐30 microM) reduced the amplitude of the M‐current in a concentration‐dependent manner, congruent to 50% inhibition of the current occurring with 1 microM‐ATP. The main effect of ATP was to reduce the maximum M‐conductance without changing the activation and deactivation kinetics of the M‐current. 5. Essentially the same results were obtained with ADP (0.1‐30 microM) and alpha, beta‐methylene‐ATP (10‐30 microM). AMP (10‐100 microM) and adenosine (10‐30 microM) were without effect on the M‐current. 6. The ATP‐induced inhibition of the M‐current was irreversible when an unhydrolysable GTP analogue GTP‐gamma‐S (10‐30 microM) was present in the pipette solution. ATP (3 microM) reduced the amplitude of the M‐current only by about 10% when GDP‐beta‐S (100 microM) was present in the pipette solution. Pre‐treatment of the cells with pertussis toxin (IAP; 500 ng ml‐1) for 24 h at 24 degrees C did not prevent the ATP‐induced M‐current inhibition. 7. Phorbol 12‐myristate 13‐acetate (PMA; 1‐3 microM) reduced the amplitude of the M‐current to about 50%. A reduction in the M‐current amplitude by PMA (3 microM) and ATP (10 microM) was attenuated when staurosporine (200 nM) was present in the pipette solution. Forskolin (10 microM) was without effect on the M‐current. 8. It is concluded that ATP acting at P2 receptors, associated with an IAP‐insensitive GTP‐binding protein, inhibits the M‐current in amphibian primary afferent neurones.