Characterization of action potential‐triggered [Ca²⁺]_i transients in single smooth muscle cells of guinea‐pig ileum

A single action potential in response to a depolarizing current pulse elicited a transient rise in [Ca²⁺]_i. When the duration of the current pulse was prolonged, action potentials were repeatedly discharged during the early period of the pulse duration with a progressive decrease in overshoot potential, upstroke rate and repolarization rate. However, such action potentials could each trigger [Ca²⁺]_i transients with an almost constant amplitude.

Nicardipine (1 μM) and La³⁺ (10 μM), blockers of voltage‐dependent Ca²⁺ channels (VDCCs), abolished both the action potential discharge and the [Ca²⁺]_i transient.

Charybdotoxin (ChTX, 300 nM) and tetraethylammonium (TEA, 2 mM), blockers of large conductance Ca²⁺‐activated K⁺ channels, decreased the rate of repolarization of action potentials but increased the amplitude of [Ca²⁺]_i transients.

Thapsigargin (1 μM), an inhibitor of SR Ca²⁺‐ATPase, slowed the falling phase and somewhat increased the amplitude, of action potential‐triggered [Ca²⁺]_i transients without affecting action potentials. In addition, in voltage‐clamped cells, the drug had little effect on the voltage step‐evoked Ca²⁺ current but exerted a similar effect on its concomitant rise in [Ca²⁺]_i to that on the action potential‐triggered [Ca²⁺]_i transient.

Similar action potential‐triggered [Ca²⁺]_i transients were induced by brief exposures to high‐K⁺ solution. They were not decreased, but rather increased, after depletion of intracellular Ca²⁺ stores by a combination of ryanodine (30 μM) and caffeine (10 mM) through an open‐lock of Ca²⁺‐induced Ca²⁺ release (CICR)‐related channels.

The results show that action potentials, discharged repeatedly during the early period of a long membrane depolarization, undergo a progressive change in configuration but can each trigger a constant rise in [Ca²⁺]_i. Intracellular Ca²⁺ stores have a role, especially in accelerating the falling phase of the action potential‐triggered [Ca²⁺]_i transients by replenishing cytosolic Ca²⁺. No evidence was provided for the involvement of CICR in the action potential‐triggered [Ca²⁺]_i transient.