The G protein G13 mediates inhibition of voltage-dependent calcium current by bradykinin
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M A Wilk-Blaszczak1, W D Singer, S Gutowski
1Department of Pharmacology, University of Texas, Southwestern Medical Center, Dallas 75235.
Abstract:
In neuroblastoma-glioma hybrid cells, bradykinin has dual modulatory effects on ion channels: it activates a K+ current as well as inhibits the voltage-dependent Ca2+ current (ICa,V). Both of these actions are mediated by pertussis toxin-insensitive G proteins. Antibodies raised against the homologous Gq and G11 proteins suppress only the activation of the K+ current; this suggested that at least two distinct G protein pathways transduce diverse effects of this transmitter. Here, we show that the inhibition of ICa,V by bradykinin is suppressed selectively by intracellular application of antibodies specific for G13. This novel G protein may play a general role in the inhibition of ICa,V by pathways resistant to pertussis toxin.
Insights
Bradykinin affects ion channels in hybrid cells by activating potassium currents and inhibiting voltage-dependent calcium currents (ICa,V). A novel G protein, G13, is identified as mediating bradykinin
Area of Science:
- Neuroscience
- Cellular Biology
- Pharmacology
Background:
- Bradykinin exerts dual effects on ion channels in neuroblastoma-glioma hybrid cells.
- These effects involve pertussis toxin-insensitive G proteins, suggesting complex signaling pathways.
- Previous studies indicated involvement of Gq and G11 proteins in K+ current activation.
Purpose of the Study:
- To elucidate the specific G protein mediating bradykinin-induced inhibition of voltage-dependent calcium current (ICa,V).
- To identify novel G protein signaling pathways involved in neurotransmitter modulation of ion channels.
Main Methods:
- Utilized neuroblastoma-glioma hybrid cells.
- Applied intracellular antibodies specific for G13 to investigate its role.
- Examined the effects of bradykinin on ion channel activity, specifically ICa,V.
Main Results:
- Bradykinin's inhibition of ICa,V was selectively suppressed by intracellular application of G13-specific antibodies.
- This finding implicates G13 as the key mediator of bradykinin's inhibitory effect on ICa,V.
- The results differentiate G13's role from Gq and G11 in ion channel modulation.
Conclusions:
- The G13 protein is identified as a novel mediator for bradykinin-induced inhibition of voltage-dependent calcium currents (ICa,V).
- This discovery highlights a new G protein signaling pathway in neurotransmitter action.
- G13 may play a broader role in inhibiting ICa,V through pertussis toxin-resistant pathways.