Correlation between G protein activation and reblocking kinetics of Ca2+ channel currents in rat sensory neurons.
Membrane depolarization relieves the G protein-mediated inhibition or block of high threshold Ca2+ channel currents. We found that the net rate of reblocking depended on the extent of G protein activation. With low intracellular concentrations of GTP gamma S reblocking rates resembled inactivation rates; with higher concentrations reblocking rates increased progressively. Reblocking kinetics were fit with a sum of two exponential functions having time constants (in ms) tau F greater than or equal to 10 and tau S greater than or equal to 30. Unblock during depolarization was fit by a single exponential function with time constant tau A similar to tau F. A model was developed in which unblocking followed dissociation of a blocking molecule, possibly the G protein itself, from Ca2+ channels, and reblocking occurred at rates that depended on the concentration of the blocking molecule. The time course of Ca2+ entry and thus presynaptic Ca2+ levels can be regulated by both the concentration of the G-protein-dependent blocking particle and membrane potential.
Lopez
H S
HS
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
Brown
A M
AM
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D019204:GTP-Binding Proteins / Q000502:physiology*; D005727:Ganglia, Spinal / Q000502:physiology; D006150:Guanine Nucleotides / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D007700:Kinetics; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D013997:Time Factors
D015220:Calcium Channels; D006150:Guanine Nucleotides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins