Related Experiment Videos
Guanine nucleotide binding proteins may modulate gating of calcium channels in vascular smooth muscle. I. Studies
Y Y Zeng1, C G Benishin, P K Pang
1Department of Physiology, University of Alberta, Edmonton, Canada.
Abstract:
Fluoride (F-), a known stimulator of G-proteins, was used to examine the relationship between G-proteins and calcium channels (CaC) in rat vascular smooth muscle (VSM). Treatment of isolated rat tail artery helical strips with F- (2.5-20 microM) produced a Ca++-dependent contraction. In the absence of added AlCl3, subthreshold NaF shifted the KCl, as well as the arginine vasopressin and norepinephrine concentration-related tension curves to the left. Nifedipine and verapamil, known CaC blockers, inhibited the NaF-related contraction. AlCl3 (20 microM), which is required for G-protein stimulation by F-, strikingly potentiated the contractile response to F-. The NaF-induced contraction was relaxed by 3-isobutyl-1-methylxanthine as well as by forskolin and by dibutyryladenosine-cyclic AMP, and the effect therefore may be independent of cAMP. 45Ca-uptake was elevated by NaF, and partially blocked by nifedipine and verapamil. NaF also inhibited the basal and forskolin-stimulated cAMP production, suggesting that F- stimulated the putative Gi in the intact VSM cells. NaF stimulated accumulation of IP in a concentration-dependent manner, indicating that F- stimulated the putative G-protein Gp which couples various receptors to hydrolysis of phosphoinositides and mobilization of Ca++. These results indicate that NaF-induced vasoconstriction is related to the opening of the CaC in the plasma membrane and perhaps a subsequent entry of the extracellular Ca++ into the cell.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Fluoride stimulates vascular smooth muscle contraction by activating G-proteins, which in turn open calcium channels. This mechanism involves increased calcium uptake and is modulated by various signaling pathways.
Area of Science:
- Physiology
- Pharmacology
- Cell Biology
Background:
- G-proteins are key regulators of cellular signaling.
- Calcium channels play a critical role in vascular smooth muscle contraction.
- Fluoride is a known activator of G-proteins.
Purpose of the Study:
- To investigate the relationship between G-proteins and calcium channels in rat vascular smooth muscle.
- To elucidate the mechanism of fluoride-induced vasoconstriction.
Main Methods:
- Isolated rat tail artery helical strips were used.
- Fluoride (NaF) and other agents (AlCl3, nifedipine, verapamil, etc.) were applied.
- Contractile responses, 45Ca-uptake, and cyclic AMP (cAMP) levels were measured.
Main Results:
- Fluoride induced a calcium-dependent contraction in vascular smooth muscle.
- Fluoride potentiated contractions and increased calcium uptake, which were inhibited by calcium channel blockers.
- Fluoride affected cAMP production and stimulated phosphoinositide hydrolysis, indicating G-protein activation.
Conclusions:
- Fluoride-induced vasoconstriction is mediated by G-protein activation of calcium channels.
- This process involves increased extracellular calcium entry into vascular smooth muscle cells.
- The findings highlight the role of G-proteins in regulating vascular tone.