Decreased calcium channel currents and facilitated epinephrine release in the Ca2+ channel beta3 subunit-null mice.
The beta subunits of voltage-dependent calcium channels are known to modify calcium channel currents through pore-forming alpha1 subunits. The beta3 subunit is expressed in the adrenal gland and participates in forming various calcium channel types. We performed a series of experiments in beta3-null mice to determine the role of the beta3 subunit in catecholamine release from the adrenal chromaffin system. Protein levels of N-type channel forming CaV2.2 and L-type forming CaV1.2 decreased. The beta3-null mice showed a decreased baroreflex, suggesting decreased sympathetic tonus, whereas plasma catecholamine levels did not change. Pulse-voltage stimulation revealed significantly increased amperometrical currents in beta3-null mice, while patch-clamp recordings showed a significant reduction in Ca(2+)-currents due to reduced L- and N-type currents, indicating facilitated exocytosis. A biochemical analysis revealed increased InsP3 production. In conclusion, our results indicate the importance of the beta3 subunit in determining calcium channel characteristics and catecholamine release in adrenal chromaffin cells.
Department of Veterinary Pharmacology, Faculty of Agriculture, Tottori University, 680-8553, Japan.
Toshio
T
Ohta
Takayoshi
T
Ohba
Takashi
T
Suzuki
Hiroyuki
H
Watanabe
Hironobu
H
Sasano
Manabu
M
Murakami
D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D017704:Baroreflex; D001794:Blood Pressure / Q000502:physiology; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D002395:Catecholamines / Q000097:blood; D019439:Chromaffin Cells / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000502:physiology*
C510225:Cacnb3 protein, mouse; D015220:Calcium Channels; D002395:Catecholamines; D015544:Inositol 1,4,5-Trisphosphate; D004837:Epinephrine