Ca²⁺-activated K⁺ channels modulate membrane potential in the human parathyroid cell: Possible role in exocytosis

The relationships between parathyroid hormone (PTH) secretion and parathyroid cell membrane potential, including the identities and roles of K⁺ channels that regulate and/or modulate membrane potential are not well defined. Here we have used Western blot/immunohistochemistry as well as patch-clamp and perifusion techniques to identify and localize specific K⁺ channels in parathyroid cells and to investigate their roles in the control of membrane potential and PTH secretion. We also re-investigated the relationship between membrane potential and exocytosis. We showed that in single human parathyroid cells K⁺ current is dependent on at least two types of Ca²⁺-activated K⁺ channels: a small-conductance Ca²⁺-activated K⁺ channel (K_SK) and a large-conductance voltage and Ca²⁺-activated K⁺ channel (K_BK). These channels were sensitive to specific peptide blocking toxins including apamin, charybdotoxin, and iberiotoxin. These channels confer sensitivity of the membrane potential in single cells to high extracellular K⁺, TEA, and peptide toxins. Blocking of K_BK potently inhibited K⁺ channel current, and K_BK was shown to be expressed in the plasma membrane of parathyroid cells. In addition, when using the capacitance technique as an indicator of exocytosis, clamping the parathyroid cell at -60 mV prevented exocytosis, whereas holding the membrane potential at 0 mV facilitated it. Taken together, the results show that human parathyroid cells have functional K_BK and K_SK channels but the data presented herein suggest that K_BK/K_SK channels likely contribute to the maintenance of the membrane potential, and that membrane potential, per se, modulates exocytosis independently of [Ca²⁺]_i.