Bovine Versus Rat Adrenal Chromaffin Cells: Big Differences in BK Potassium Channel Properties

Abstract

Both bovine and rat adrenal chromaffin cells have served as pioneering model systems in cellular neurophysiology, including in the study of large conductance calcium- and voltage-dependent K(+) (BK) channels. We now report that while BK channels dominate the outward current profile of both species, specific gating properties vary widely across cell populations, and the distributions of these properties differ dramatically between species. Although BK channels were first described in bovine chromaffin cells, rapidly inactivating ones were discovered in rat chromaffin cells. We report that bovine cells can also exhibit inactivating BK channels with varying properties similar to those in rat cells. However, a much smaller proportion of bovine cells exhibit inactivating BK current, the proportion of the total current that inactivates is usually smaller, and the rate of inactivation is often much slower. Other gating features differ as well; the voltage dependence of channel activation is much more positive for bovine cells, and their rates of activation and deactivation are faster and slower, respectively. Modeling studies suggest that channel heterogeneity is consistent with varying tetrameric combinations of inactivation-competent versus -incompetent subunits. The results suggest that chromaffin BK channel functional nuances represent an important level for evolutionary tailoring of autonomic stress responses.

Pituitary Control of BK Potassium Channel Function and Intrinsic Firing Properties of Adrenal Chromaffin Cells

“…2 A, top four traces) recorded from a small hypox patch exhibiting a mixed-BK phenotype reveals at least three to four BK i channels and at least one sustained or very slowly inactivating BK s channel. In agreement with previous reports for normal rat chromaffin cells Lovell et al 2000), single-channel conductances for both channel types were calculated to be ϳ270 pS (in symmetrical K ϩ ). An ensemble average of 16 traces (Fig.…”

“…Similar to what has been described previously for normal rat cells (Neely and Lingle, 1992a,b;Solaro et al, 1995;Lovell et al 2000), the majority (67.1%) of hypox patches were found to express the rapid and completely inactivating variant of BK (Fig. 4 A, top left trace), whereas smaller proportions exhibited the more slowly inactivating mixed current (24.4%; n ϭ 20; Fig.…”

“…Thus in individual cells, BK channels may be composed of varying proportions of STREX and ZERO-like subunits (as well as ␤ subunits) as determined by a binomial expansion from the percentages of starting subunits. Lovell et al (2000) and Ding et al (1998) have argued that a similar model can accurately predict the broad range of BK channel inactivation rates that has been observed in both the rat and bovine chromaffin cell population (see description below).…”

“…The rate and extent of inactivation have been shown to vary dramatically across chromaffin cell populations of rat and bovine, as well as between the species Lingle et al, 1996;Lovell et al, 2000). In oocytes coinjected with Slo cRNA, at least two distinct but related accessory subunits can confer rapid inactivation that is similar to that in native chromaffin cells (Wallner et al, 1999;Xia et al, 1999Xia et al, , 2000Uebele et al, 2000).…”

“…Thus the intrinsic excitable properties of chromaffin cells, by defining action potential responses, play perhaps as great a role in limiting or patterning epinephrine secretion as does the input. In chromaffin cells, a significant fraction of the outward current gated at physiological voltages is carried by BK (big K ϩ ) voltage-and Ca 2ϩ -activated potassium channels, leading several investigators to argue that BK channels play a central role in shaping intrinsic excitability, particularly with respect to repetitive firing Lingle et al, 1996;Lovell et al, 2000). Recent evidence that pituitary stress hormones influence alternative splicing of Slo gene-encoded BK channels has raised the hypothesis that stressrelated activation of the hypothalamic-pituitary-adrenocortical (HPA) axis may dynamically control the character of autonomic crisis responses by tuning chromaffin cell excitability (Xie and McCobb, 1998).…”