Voltage-dependent phosphorylation may recruit Ca2+ current facilitation in chromaffin cells.
Bovine chromaffin cells have two components of whole-cell Ca2+ current: 'standard' Ca2+ currents that are activated by brief depolarizations, and 'facilitation' Ca2+ currents, which are normally quiescent but can be activated by large pre-depolarizations or by repetitive depolarizations to physiological potentials. The activation of protein kinase A can also stimulate Ca2+ current facilitation, indicating that phosphorylation can play a part in facilitation. Here we investigate the role of protein phosphorylation in the recruitment of facilitation Ca2+ currents by pre-pulses or repetitive depolarizations. We find that recruitment of facilitation by depolarization is a rapid first-order process which is suppressed by inhibitors of protein phosphorylation or by injection of phosphatase 2A into cells. Recruitment of facilitation Ca2+ current by voltage is normally reversible but phosphatase inhibitors render it irreversible. Our results indicate that recruitment of these Ca2+ currents by pre-pulses or repetitive depolarizations involves voltage-dependent phosphorylation of the facilitation Ca2+ channel or a closely associated regulatory protein. Voltage-dependent phosphorylation may therefore be a mechanism by which membrane potential can modulate ion channel activity.
Artalejo
C R
CR
Department of Pharmacological and Physiological Sciences, University of Chicago, Illinois 60637.
Rossie
S
S
Perlman
R L
RL
Fox
A P
AP
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000255:Adenosine Triphosphate / Q000378:metabolism; D000313:Adrenal Medulla / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D002417:Cattle; D004988:Ethers, Cyclic / Q000494:pharmacology; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007546:Isoquinolines / Q000494:pharmacology; D008564:Membrane Potentials; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D054648:Protein Phosphatase 2
D015220:Calcium Channels; D004988:Ethers, Cyclic; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D019319:Okadaic Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000255:Adenosine Triphosphate; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D002118:Calcium