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Selectivity of omega-CgTx-MVIIC toxin from Conus magus on calcium currents in enteric neurons
1Department of Physiology, College of Medicine, The Ohio State University, Columbus 43210-1218, USA.
Abstract:
Whole-cell perforated patch clamp recordings were used to analyze selectivity of omega-CgTx-MVIIC toxin for voltage-dependent calcium currents in cultured myenteric neurons from guinea-pig small intestine. Omega-CgTx-MVIIC (300 nM) blocked 37 +/- 9% of the peak current activated from -80 mV in 15 neurons by mostly affecting the plateau phase of the current. The toxin suppressed peak current activated from -30 mV dose-dependently with an IC50 of 70 +/- 8 nM. The blockade was complete at toxin concentrations of 1 microM. Thus, it appears that omega-CgTx-MVIIC blocks high voltage activated (HVA) calcium channels in the myenteric neurons unselectively as well as other types of HVA Ca2+ channels including P and Q channels.
Insights
Omega-conotoxin-MVIIC (omega-CgTx-MVIIC) toxin affects high voltage-activated calcium channels in guinea-pig myenteric neurons. This toxin unselectively blocks these calcium channels, impacting neuronal function.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Physiology
Background:
- The myenteric plexus, a component of the enteric nervous system, regulates gastrointestinal function.
- Voltage-dependent calcium channels (VDCCs) play crucial roles in neuronal excitability and neurotransmitter release.
- Omega-conotoxins are peptides known to modulate various ion channels, including calcium channels.
Purpose of the Study:
- To investigate the selectivity of omega-conotoxin-MVIIC (omega-CgTx-MVIIC) for specific high voltage-activated (HVA) calcium currents in cultured myenteric neurons.
- To characterize the dose-dependent effects of omega-CgTx-MVIIC on calcium currents in these neurons.
Main Methods:
- Whole-cell perforated patch clamp recordings were performed on cultured myenteric neurons from guinea-pig small intestine.
- The effects of varying concentrations of omega-CgTx-MVIIC on calcium currents activated at different potentials were analyzed.
Main Results:
- Omega-CgTx-MVIIC (300 nM) inhibited 37 +/- 9% of the peak calcium current activated from -80 mV, primarily affecting the plateau phase.
- The toxin dose-dependently suppressed peak current activated from -30 mV, with a calculated IC50 of 70 +/- 8 nM.
- Complete blockade of calcium currents was observed at omega-CgTx-MVIIC concentrations of 1 microM.
Conclusions:
- Omega-CgTx-MVIIC exhibits unselective blockade of high voltage-activated (HVA) calcium channels in guinea-pig myenteric neurons.
- The findings suggest that omega-CgTx-MVIIC can affect multiple types of HVA calcium channels, including P- and Q-type channels, in these neurons.