Characterization and regulation of Ca²⁺-dependent K⁺ channels in human esophageal smooth muscle

Abstract

We examined the properties of K+ channels in smooth muscle cells dissociated from human esophagus using patch-clamp recording in the cell-attached configuration. The predominant channel observed had a conductance of 224 ± 4 pS, and current reversal was dependent on K+ concentration. Channel activity was voltage dependent and increased with elevation of intracellular free Ca2+ concentration ([Ca2+]i), consistent with this being the large-conductance Ca2+-dependent K+(KCa) channel. ACh as well as caffeine caused transient increases in KCa channel activity, and the effects of ACh persisted in Ca2+-free solution, indicating that Ca2+ release from stores contributed to channel activation. Simultaneous patch clamp and fluorescence revealed that KCachannel activity was well correlated with elevation of [Ca2+]i. The functional role of KCachannels in esophagus was studied by measuring ACh-induced contraction of strips of muscle. Tetraethylammonium and iberiotoxin, blockers of KCa channels, increased ACh-induced contraction, consistent with a role for K+ channels in limiting excitation and contraction. These studies are the first to characterize KCa channels and their regulation in human esophageal smooth muscle.

Characterization of a voltage-dependent Na+current in human esophageal smooth muscle

“…1F; n ϭ 6). The properties and regulation of the K v and K Ca currents described here resemble those reported earlier (21,32), further validating the use of this culture system.…”

Resting Potential and Submembrane Calcium Concentration of Inner Hair Cells in the Isolated Mouse Cochlea Are Set by KCNQ-Type Potassium Channels

“…Surprisingly, the BK channels of IHCs showed particularly negative activation ranges. Thus, the voltage required for half-maximal activation at [Ca 2ϩ ] i of 1 M was ϩ7 mV, whereas it can be as positive as ϩ50 to 100 mV in other cell types and expression systems (Cui et al, 1997;Hurley et al, 1999). Accordingly, low micromolar concentrations of Ca 2ϩ are sufficient to allow for substantial BK channel activation in IHCs on the working voltage range of these nonspiking cells.…”

α5β1 Integrin Engagement Increases Large Conductance, Ca2+-activated K+ Channel Current and Ca2+ Sensitivity through c-src-mediated Channel Phosphorylation

“…Large conductance, Ca 2ϩ -activated K ϩ channels (BK, 3 Maxi-K) represent a subset of the superfamily of K ϩ -selective ion channels widely expressed in neurons, smooth muscle, and other tissues. In vascular smooth muscle (VSM), BK channels are important targets of endothelium-derived vasoactive factors, and their activation by depolarization and/or increases in intracellular calcium leads to smooth muscle hyperpolarization and vasodilation (1)(2)(3)(4).…”

“…In vascular smooth muscle (VSM), BK channels are important targets of endothelium-derived vasoactive factors, and their activation by depolarization and/or increases in intracellular calcium leads to smooth muscle hyperpolarization and vasodilation (1)(2)(3)(4). This sequence of events serves as a negative feedback mechanism to limit Ca 2ϩ entry by closure of voltage-dependent Ca 2ϩ channels (5).…”