Modulation of Ca-channel current by an adenosine analog mediated by a GTP-binding protein in chick sensory neurons.
Inhibitory modulation of the high-voltage-activated (HVA) Ca-channel current by 2-chloroadenosine (2CA) was studied in chick sensory neurons using the whole-cell clamp method. 2CA reduced the omega CTX-sensitive HVA-current (Aosaki and Kasai 1989) in a dose-dependent manner with a Kd of 0.8 microM. The inhibition by 2CA was also voltage-dependent, being maximal at hyperpolarized potentials, and completely removed at potentials more positive than 30 mV. This voltage-dependence of 2CA action was also evident as a progressive increase in Ca-channel current magnitude during a depolarization which could be described by a single exponential function and which became faster at larger depolarizations. The concentration of 2CA affected the steady-state reduction in Ca-channel current, but did not alter the time-course of current increase during depolarization. The voltage-dependent effect of 2CA was mimicked by intracellular application of GTP-gamma S, but not by phorbol ester, arachidonic acid or nitroprusside. These results are consistent with model in which 2CA activates a G-protein, which then unmasks an additional activation gate on the Ca-channel.
Kasai
H
H
Department of Physiology, Faculty of Medicine, University of Tokyo, Japan.
Aosaki
T
T
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D002642:Chick Embryo; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D008978:Mollusk Venoms / Q000494:pharmacology; D009475:Neurons, Afferent / Q000378:metabolism*; D015290:Second Messenger Systems; D013873:Thionucleotides / Q000494:pharmacology; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D008978:Mollusk Venoms; D013873:Thionucleotides; D020960:omega-Conotoxins; C053423:Conus magus toxin; D015762:2-Chloroadenosine; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D000241:Adenosine