Bile Acid Inhibition of N-type Calcium Channel Currents from Sympathetic Ganglion Neurons.
10.4196/kjpp.2012.16.1.25
- Author:
Hye Kyung LEE
1
;
Kyoung Hwa LEE
;
Eui Sic CHO
Author Information
1. Department of Pharmacology, University of Ulsan College of Medicine, Seoul 138-736, Korea. kyung@amc.seoul.kr
- Publication Type:Original Article
- Keywords:
Bile acid;
Cholic acid;
N-type Ca2+ channel;
Sympathetic ganglion
- MeSH:
Bile;
Bile Acids and Salts;
Calcium Channels, N-Type;
Cell Membrane;
Central Nervous System;
Cholic Acid;
Enterohepatic Circulation;
Fees and Charges;
Ganglia, Sympathetic;
Liver Diseases;
Nervous System;
Neurons;
Neurotransmitter Agents;
Plasma;
Rana catesbeiana;
Synapses
- From:The Korean Journal of Physiology and Pharmacology
2012;16(1):25-30
- CountryRepublic of Korea
- Language:English
-
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 Ca2+ channel that is essential for neurotransmitter release at synapses of the peripheral and central nervous system. N-type Ca2+ channel currents were recorded from bullfrog sympathetic neuron under a cell-attached mode using 100 mM Ba2+ 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 Ca2+ channel, which appeared to be due to an increase in null (no activity) sweeps. For example, the proportion of null 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 Ca2+ 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 Ca2+ channel function may be beneficial against overexcitation of the synapses.
