Activation of K+ channels by lanthanum contributes to the block of transmitter release in chick and rat sympathetic neurons.
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 microM) 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 Ca(2+)-channel blockers cadmium and verapamil, which never blocked more than 70% of the release. At 3 microM, 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 microM La3+. However, 3 microM La3+ produced only a partial block of voltage clamped Ca2+ current (ICa). Following La3+ (10 microM) treatment 3H-NE release could be evoked by high K+ stimulation of neurons which were refractory to electrical stimulation. La3+ (1 microM) increased the hyperpolarization activated, 4-aminopyridine (4-AP) sensitive, transient K+ current (IA) 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.
Przywara
D A
DA
Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Bhave
S V
SV
Bhave
A
A
Chowdhury
P S
PS
Wakade
T D
TD
Wakade
A R
AR
D000320:Adrenergic Fibers / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002642:Chick Embryo; D004553:Electric Conductivity; D004558:Electric Stimulation; D007811:Lanthanum / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D014700:Verapamil / Q000494:pharmacology
D015221:Potassium Channels; D002104:Cadmium; D007811:Lanthanum; D014700:Verapamil; D002118:Calcium; D009638:Norepinephrine