Voltage-activated ion channels and Ca(2+)-induced Ca (2+) release shape Ca (2+) signaling in Merkel cells.
Ca(2+) 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 Ca(2+) signaling in purified Merkel cells. Merkel cells in the intact skin were specifically labeled by antibodies against voltage-activated Ca(2+) channels (Ca(V)2.1) and voltage- and Ca(2+)-activated K(+) (BK(Ca)) channels. Voltage-clamp recordings revealed small Ca(2+) currents, which produced Ca(2+) transients that were amplified sevenfold by Ca(2+)-induced Ca(2+) release. Merkel cells' voltage-activated K(+) currents were carried predominantly by BK(Ca) channels with inactivating and non-inactivating components. Thus, Merkel cells, like hair cells, have functionally diverse BK(Ca) channels. Finally, blocking K(+) channels increased response magnitude and dramatically shortened Ca(2+) transients evoked by mechanical stimulation. Together, these results demonstrate that Ca(2+) signaling in Merkel cells is governed by the interplay of plasma membrane Ca(2+) channels, store release and K(+) channels, and they identify specific signaling mechanisms that may control touch sensitivity.
Piskorowski
Rebecca
R
Department of Physiology, University of California, San Francisco, CA 94143, USA.
Haeberle
Henry
H
Panditrao
Mayuri V
MV
Lumpkin
Ellen A
EA
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002469:Cell Separation; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004594:Electrophysiology; D049452:Green Fluorescent Proteins / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology; D018862:Merkel Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018408:Patch-Clamp Techniques; D020133:Reverse Transcriptase Polymerase Chain Reaction
D051792:Basic Helix-Loop-Helix Proteins; D002118:Calcium; D018118:Chloride Channels; D018076:DNA, Complementary; D049452:Green Fluorescent Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels; C500943:Atoh1 protein, mouse