Persistent calcium-sensitive potassium current and the resting properties of guinea-pig myenteric neurones

1. Intracellular recordings were made from neurones in the guinea-pig myenteric plexus which show a long-lasting after-hyperpolarization following the action potential (AH neurones). In most experiments membrane currents were measured using a single-electrode voltage clamp. Tetrodotoxin was present. 2. A step depolarization (10-15 mV, 5-10 s) from a holding potential close to the resting level (typically -60 mV) caused a slowly developing outward current. The current increased exponentially with a time constant of about 1.3 s at -50 mV. At the termination of the step the current declined over a similar time period (time constant congruent to 2.5 s). Hyperpolarizing step commands resulted in a slowly declining outward current (tau congruent to 3.5 s at -70 mV) which developed again at the termination of the hyperpolarization (tau congruent to 2.1 s at -60 mV); these tail currents reversed at the potassium equilibrium potential. 3. The current was not observed in solutions containing no calcium, high magnesium concentrations and cobalt. It did not inactivate during changes in holding potential of up to 5 min. The current is therefore called the persistent calcium-sensitive potassium current. 4. A brief depolarizing command to less-negative potentials (typically to -10 mV for 10-30 ms) was followed by a potassium current which increased and decreased according to the sum of two exponentials having time constants tau on congruent to 0.4 s and tau off congruent to 2.5 s. This after-current disappeared in calcium-free, high-magnesium and cobalt solution. 5. Both the after-current and the persistent calcium-sensitive current were similarly sensitive to tetraethylammonium ions, being unaffected by 5 mM but substantially reduced by 20 mM solutions. The time constant of decline of the persistent calcium-sensitive current at the end of a depolarizing step was not different from tau off for the after-current; these time constants had a similar sensitivity to voltage and temperature. 6. The conductance underlying the after-current became progressively smaller as the persistent calcium-sensitive current was increased by membrane depolarization. In a given neurone, the sum of the two conductances was constant. This finding implies that the persistent calcium-sensitive potassium conductance is the same conductance as that which is increased during the after-hyperpolarization.