BK_Ca currents are enriched in a subpopulation of adult rat cutaneous nociceptive dorsal root ganglion neurons

Abstract

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 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 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. RT-PCR analysis of mRNA collected from whole DRG revealed the presence of multiple splice variants of the BK Ca channel α-subunit, rslo and all 4 of the accessory β 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 β 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.

Inhibition of Inflammatory Pain by Activating B-Type Natriuretic Peptide Signal Pathway in Nociceptive Sensory Neurons

“…6 A), indicating BK Ca channels may not open under this condition, consistent with a previous report that BK Ca current in DRG neurons is dependent on Ca 2ϩ influx via voltage-gated Ca 2ϩ channels (X. L. Zhang et al, 2010). This result further suggests that it is BK Ca channels to mediate BNP action, because BNP could not regulate the triggered current when BK Ca channels were not opened.…”

“…Electrophysiological recording showed that the triggered current in all examined small DRG neurons were suppressed by BK Ca channel inhibitor IBTX, consistent with previous report that BK Ca current are present in the vast majority of small DRG neurons (X. L. Zhang et al, 2010). Immunochemistry showed BK Ca channels were present in almost all small DRG neurons of rats (cross-sectional area, Ͻ900 m 2 ), including CGRP-and IB4-positive neurons (Fig.…”

“…Previous studies have shown that activation of NPR-A induces cGMP synthesis, and activates downstream PKG, which phosphorylates large-conductance Ca 2ϩ -activated K ϩ channels (BK Ca channels) and increases their open probability, leading to the hyperpolarization of vascular smooth muscle cells and glomerular mesangial cells (Williams et al, 1988;Sansom and Stockand, 1996;Tanaka et al, 1998). Importantly, BK Ca current is present in the vast majority of small DRG neurons and contributes to the repolarization of the action potential (X. L. Zhang et al, 2010). Moreover, BK Ca channel opener NS1619 reduces firing frequency of small DRG neurons (X. F. Zhang et al, 2003).…”

“…6 A). BK Ca current was isolated by taking the difference between total current and IBTX-resistant current (X. L. Zhang et al, 2010). Bath application of BNP (100 ng/ml) for 10 min before IBTX treatment resulted in an enlarged current with 13.7 Ϯ 2.4% increase, compared with the current before BNP treatment (at 100 mV; p Ͻ 0.001; 12 of 21 neurons) (Fig.…”

Sex differences in the inflammatory mediator-induced sensitization of dural afferents

“…For example, an IM-induced increase in K ϩ conductance may have masked the impact of an increase in TTX-R I Na in unresponsive male dural afferents. We and others have described an IM-induced increase in intracellular Ca 2ϩ in dural afferents as well as evidence of several different Ca 2ϩ -modulated/dependent K ϩ currents in sensory neurons (Gold et al 1996b;Vaughn and Gold 2010;Zhang et al 2010), suggesting that a substrate for such an increase in K ϩ current is present in dural afferents. Given the absence of a detectable decrease in R I and/or depolarization of membrane potential in unresponsive neurons, a more likely explanation for the absence of sensitization of a subpopulation of male dural afferents is a lack of I IM-Cl activation in these neurons, underscoring the importance of this conductance to the IM-induced sensitization of dural afferents.…”