Ethanol reduces excitability in a subgroup of primary sensory neurons by activation of BK(Ca) channels.
Ethanol effects on the central nervous system have been well investigated and described in recent years; modulations, by ethanol, of several ligand-gated and voltage-gated ion channels have been found. In this paper, we describe a shortening of action potential duration (APD) by ethanol in approximately equal to 40% of small diameter neurons in rat dorsal root ganglia (DRG). In these neurons, designated as group A neurons, we observed an ethanol-induced increase in whole-cell outward-current. As iberiotoxin, a specific blocker of large-conductance calcium-activated K+ channels (BK(Ca) channels), blocks the effects of ethanol, we investigated the interaction between these channels and ethanol in outside-out patches. Open probability of BK(Ca) channels was increased 2-6 x depending on the concentration (40-80 mM approximately equal to 2-4 per thousand v/v) of ethanol. Functional consequences were a prolongation of the refractory period, which was reversible after addition of iberiotoxin, and reduced firing frequency during ethanol application. In contrast, another type of neuron (group B) showed a prolonged APD during application of ethanol which was irreversible in most cases. In 90% of cases, neurons of group A showed a positive staining for isolectin B4 (I-B4), a marker for nociceptive neurons. We suggest that the activation of BK(Ca) channels induced by clinically relevant concentrations of ethanol, the resulting modulations of APD and refractory period of DRG neurons, might contribute to clinically well-known ethanol-induced analgesia and paresthesia.
Gruss
M
M
Physiologisches Institut, Justus-Liebig-Universität, 35385 Giessen, Germany.
Henrich
M
M
König
P
P
Hempelmann
G
G
Vogel
W
W
Scholz
A
A
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D009924:Organ Culture Techniques; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology
D002614:Chelating Agents; D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; D000431:Ethanol; D004533:Egtazic Acid; C064719:iberiotoxin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium