Co-ordinated modulation of Ca²⁺ and K⁺ currents during ascidian muscle development

1. The development of Ca²⁺ and K⁺ currents was studied in ascidian muscle cells at twelve embryonic stages from gastrulation to the mature cell, a period of 24 h. A high degree of co-ordination occurs between the development of the inwardly rectifying K⁺ current (I(K(IR))), which sets the resting potential, and Ca²⁺ and outward K⁺ currents, which determine action potential, waveform. 2. At neurulation I(K(IR)), which had been present since fertilization, begins to decrease, reaching 12% of its previous density in 6 h. I(K(IR)) then immediately begins to increase again, reaching its previous density in another 6 h. 3. When I(K(IR)) begins to decrease, a high-threshold inactivating Ca²⁺ current and a slowly activating voltage-gated K⁺ current appear. 4. When I(K(IR)) returns to its previous density, two new currents appear: a sustained Ca²⁺ current with the same voltage dependence, but different conotoxin sensitivity than the inactivating Ca²⁺ current; and a Ca²⁺-dependent K⁺ current, which activates 8-10 times faster and at potentials 20-30 mV more negative than the voltage-dependent K⁺ current. 5. The transient downregulation of I(K(IR)) destabilizes the resting potential and causes spontaneous action potentials to occur. Because I(K(IR)) is absent when only a slowly activating high-threshold outward K⁺ current is present, these action potentials are long in duration. 6. The return of I(K(IR)) and the appearance of the rapidly activating Ca₂₊-dependent K⁺ current eventually terminate this activity. The action potentials of the mature cell occur only on stimulation, and are 10 times shorter in duration than those in the immature cell.