Voltage-activated ion channels and Ca2+-induced Ca2+ release shape Ca2+ signaling in Merkel cells

Ca2+ signaling and neurotransmission modulate touch-evoked responses in Merkel cell–neurite complexes. To identify mechanisms governing these processes, we analyzed voltage-activated ion channels and Ca2+ signaling in purified Merkel cells. Merkel cells in the intact skin were specifically labeled by antibodies against voltage-activated Ca2+ channels (CaV2.1) and voltage- and Ca2+-activated K+ (BKCa) channels. Voltage-clamp recordings revealed small Ca2+ currents, which produced Ca2+ transients that were amplified sevenfold by Ca2+-induced Ca2+ release. Merkel cells’ voltage-activated K+ currents were carried predominantly by BKCa channels with inactivating and non-inactivating components. Thus, Merkel cells, like hair cells, have functionally diverse BKCa channels. Finally, blocking K+ channels increased response magnitude and dramatically shortened Ca2+ transients evoked by mechanical stimulation. Together, these results demonstrate that Ca2+ signaling in Merkel cells is governed by the interplay of plasma membrane Ca2+ channels, store release and K+ channels, and they identify specific signaling mechanisms that may control touch sensitivity.