Short-term regulation of neuronal calcium channels by depolarization.
The 1,4-dihydropyridine-sensitive voltage-gated Ca2+ channel is widely distributed in excitable cells. The channel and its several associated drug binding sites are known to be up- and downregulated by a variety of homologous and heterologous influences including membrane depolarization. The neurosecretory GH4C1 cell line possesses L-type channels. Depolarization of these cells by elevated K+ increases the binding affinity of 1,4-dihydropyridines and decreases the number of 1,4-dihydropyridine binding sites and functional channels. There is a coordinate upregulation of the number of muscarinic receptors. This membrane potential- and Ca(2+)-calmodulin-dependent process of channel downregulation may involve internalization of the channel heteromeric complex or, more plausibly, a dissociation of the complex and a concomitant loss of both binding and permeation functions.
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D020746:Calcium Channels, L-Type; D002460:Cell Line; D004095:Dihydropyridines / Q000378:metabolism / Q000494:pharmacology; D015536:Down-Regulation; D006706:Homeostasis; D015640:Ion Channel Gating; D017275:Isradipine / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D008954:Models, Biological; D019832:N-Methylscopolamine; D009474:Neurons / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D012602:Scopolamine Derivatives / Q000378:metabolism; D015854:Up-Regulation
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D008565:Membrane Proteins; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; C038806:1,4-dihydropyridine; D011188:Potassium; D002118:Calcium; D019832:N-Methylscopolamine; D017275:Isradipine