The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Bile Acid Inhibition of N-type Calcium Channel Currents from Sympathetic Ganglion Neurons

  • Lee, Hye-Kyung (Department of Pharmacology, University of Ulsan College of Medicine) ;
  • Lee, Kyoung-Hwa (Laboratory for Craniofacial Research, Chonbuk National University Dental School) ;
  • Cho, Eui-Sic (Laboratory for Craniofacial Research, Chonbuk National University Dental School)
  • Received : 2011.10.11
  • Accepted : 2012.01.08
  • Published : 2012.02.29
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Abstract

Under some pathological conditions as bile flow obstruction or liver diseases with the enterohepatic circulation being disrupted, regurgitation of bile acids into the systemic circulation occurs and the plasma level of bile acids increases. Bile acids in circulation may affect the nervous system. We examined this possibility by studying the effects of bile acids on gating of neuronal (N)-type $Ca^{2+}$ channel that is essential for neurotransmitter release at synapses of the peripheral and central nervous system. N-type $Ca^{2+}$ channel currents were recorded from bullfrog sympathetic neuron under a cell-attached mode using 100 mM $Ba^{2+}$ as a charge carrier. Cholic acid (CA, $10^{-6}M$) that is relatively hydrophilic thus less cytotoxic was included in the pipette solution. CA suppressed the open probability of N-type $Ca^{2+}$ channel, which appeared to be due to an increase in (no activity) sweeps. For example, the proportion of sweep in the presence of CA was ~40% at +40 mV as compared with ~8% in the control recorded without CA. Other single channel properties including slope conductance, single channel current amplitude, open and shut times were not significantly affected by CA being present. The results suggest that CA could modulate N-type $Ca^{2+}$ channel gating at a concentration as low as $10^{-6}M$. Bile acids have been shown to activate nonselective cation conductance and depolarize the cell membrane. Under pathological conditions with increased circulating bile acids, CA suppression of N-type $Ca^{2+}$ channel function may be beneficial against overexcitation of the synapses.

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