Modulation of type A K+ current inDrosophila larval muscle by internal Ca2+; effects of the overexpression of frequenin
We studied the effects of lanthanum (La3+) on the release of 3H-norepinephrine(3H-NE), intracellular Ca2+ concentration, and voltage clamped Ca2+ and K+ currents in cultured sympathetic neurons. La3+ (0.1 to 10 μm) produced concentration-dependent inhibition of depolarization induced Ca2+ influx and 3H-NE release. La3+ was more potent and more efficacious in blocking 3H-NE release than the Ca2+-channel blockers cadmium and verapamil, which never blocked more than 70% of the release. At 3 μm, La3+ produced a complete block of the electrically stimulated rise in intracellular free Ca2+ ([Ca2+] i ) in the cell body and the growth cone. The stimulation-evoked release of 3H-NE was also completely blocked by 3 μm La3+. However, 3 μm La3+ produced only a partial block of voltage clamped Ca2+ current (I Ca). Following La3+ (10 μm) treatment 3H-NE release could be evoked by high K+ stimulation of neurons which were refractory to electrical stimulation. La3+ (1 μm) increased the hyperpolarization activated, 4-aminopyridine (4-AP) sensitive, transient K+ current (I A ) with little effect on the late outward current elicited from depolarized holding potentials. We conclude that the effective block of electrically stimulated 3H-NE release is a result of the unique ability of La3+ to activate a stabilizing, outward K+ current at the same concentration that it blocks inward Ca2+ current.