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Concentration dependence of neurotransmitter effects on calcium current kinetics in frog sympathetic neurones.
Author(s) -
Elmslie K S,
Jones S W
Publication year - 1994
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1994.sp020417
Subject(s) - neurotransmitter , calcium , kinetics , chemistry , biophysics , current (fluid) , neuroscience , medicine , endocrinology , biology , central nervous system , physics , organic chemistry , quantum mechanics , thermodynamics
1. Noradrenaline (NA) slows the activation kinetics of N‐type calcium channels, via G proteins. It has been suggested that the G proteins act by binding directly to the calcium channels. If the slow kinetics reflect binding and unbinding of G proteins, the rates should depend on the concentration of activated G protein. 2. We used different concentrations of NA, and increasing durations of intracellular dialysis with GTP‐gamma‐S, to vary the concentration of activated G protein. 3. At depolarized potentials (‐20 or ‐10 mV), the slow activation kinetics showed no detectable concentration dependence. This analysis required correction for effects of inactivation on the measured time constants. 4. At ‐80 mV, reinhibition of calcium channel current was more rapid for larger responses. Thus, the effect appears to be concentration dependent at ‐80 mV, but not at more depolarized voltages. 5. This voltage dependence is actually expected from kinetic principles: the binding step is rate limiting when the position of equilibrium is toward the bound state (at ‐80 mV), but not when equilibrium favours unbinding (when the channel is open). 6. During inhibition, the channel appears to ‘sense’ directly the concentration of the modulator, possibly active G proteins.