BKCa currents are enriched in a subpopulation of adult rat cutaneous nociceptive dorsal root ganglion neurons.
The biophysical properties and distribution of voltage-dependent, Ca(2+) -modulated K(+) (BK(Ca)) currents among subpopulations of acutely dissociated DiI-labeled cutaneous sensory neurons from the adult rat were characterized with whole-cell patch-clamp techniques. BK(Ca) currents were isolated from total K(+) current with iberiotoxin, charybdotoxin or paxilline. There was considerable variability in biophysical properties of BK(Ca) currents. There was also variability in the distribution of BK(Ca) current among subpopulations of cutaneous dorsal root ganglia (DRG) neurons. While present in each of the subpopulations defined by cell body size, IB4 binding or capsaicin sensitivity, BK(Ca) current was present in the vast majority (> 90%) of small-diameter IB4+ neurons, but was present in only a minority of neurons in subpopulations defined by other criteria (i.e. small-diameter IB4-). Current-clamp analysis indicated that in IB4+ neurons, BK(Ca) currents contribute to the repolarization of the action potential and adaptation in response to sustained membrane depolarization, while playing little role in the determination of action potential threshold. Reverse transcriptase-polymerase chain reaction analysis of mRNA collected from whole DRG revealed the presence of multiple splice variants of the BK(Ca) channel alpha-subunit, rslo and all four of the accessory beta-subunits, suggesting that heterogeneity in the biophysical and pharmacological properties of BK(Ca) current in cutaneous neurons reflects, at least in part, the differential distribution of splice variants and/or beta-subunits. Because even a small decrease in BK(Ca) current appears to have a dramatic influence on excitability, modulation of this current may contribute to sensitization of nociceptive afferents observed following tissue injury.
Zhang
Xiu-Lin
XL
Department of Biomedical Sciences, Dental School, University of Maryland, Baltimore, MD 21201, USA.
Mok
Lee-Peng
LP
Katz
Elizabeth J
EJ
Gold
Michael S
MS
D017398:Alternative Splicing; D000818:Animals; D048430:Cell Shape; D005727:Ganglia, Spinal / Q000166:cytology*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D008297:Male; D009619:Nociceptors / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D015221:Potassium Channels; D021122:Protein Subunits