Calcium-activated, voltage-dependent K+ (BK) channels account for differences in the spiking pattern between spontaneously active rat somatotrophs, lactotrophs and gonadotrophs

Abstract

Rat anterior pituitary cells exhibit spontaneous and extracellular Ca2+-dependent fluctuations in intracellular Ca2+ concentration ([Ca2+]i), the pattern of which differs among the cell types. In somatotrophs and lactotrophs, large amplitude Ca2+ fluctuations are observed, whereas small amplitude fluctuations occur in gonadotrophs. Consistent with this, different patterns of electrical activity were observed in the three cell types using perforated patch-clamp techniques. In somatotrophs and lactotrophs, electrical activity was characterized by transient membrane depolarizations, during which multiple spikes of low amplitude were observed. In contrast, single, high amplitude spikes characterized the firing pattern in gonadotrophs. One channel that may dictate the different patterns of action potential firing is the Ca2+-activated, voltage-dependent K+ (BK) channel. RT-PCR analysis indicated the expression of BK channels in these cells. The functional expression of BK channels in each cell type was examined and compared in current-clamped cells. In all three cell-types, activation of L-type Ca2+ channels and the concomitant increase in [Ca2+]i activated a K+ current, which was abolished by specific BK channel inhibitors. Although voltage-gated Ca2+ entry activated BK channels in all three cell-types, the magnitude of current activation was much greater in somatotrophs and lactotrophs than in gonadotrophs. Accordingly, the contribution of BK channels to the action potential profile was more prominent in somatotrophs and lactotrophs than in gonadotrophs. In somatotrophs and lactotrophs, BK channels mediated the number and amplitude of spikes during each burst and the amplitude of the associated [Ca2+]i transients. In contrast, BK channels did not contribute to spiking activity or [Ca2+]i oscillations in gonadotrophs. Thus, differences in the firing patterns and associated Ca2+ entry between somatotrophs/lactotrophs and gonadotrophs may be due to differential expression and/or activation of BK channels.