Volume-activated chloride currents in interstitial cells of Cajal

Author:

Park Sung Jin,Mckay Catherine M.,Zhu Yaohui,Huizinga Jan D.

Abstract

Interstitial cells of Cajal (ICC) undergo marked morphological changes on contraction of the musculature, making it essential to understand properties of mechanosensitive ion channels. The whole cell patch-clamp technique was used to identify and to characterize volume-activated Cl currents in ICC cultured through the explant technique. Hypotonic solutions (≈210 mosM) activated an outwardly rectifying current, which reversed near the equilibrium potential for Cl. Time-dependent inactivation occurred only at pulse potentials of +80 mV, with a time constant of 478 ± 182 ms. The degree of outward rectification was calculated using a rectification index, the ratio between the slope conductances of +65 and −55 mV, which was 13.9 ± 1.5 at 76 mM initial extracellular Cl concentration. The sequence of relative anion permeability of the outwardly rectifying Cl channel was I > Cl > aspartate. The chloride channel blockers, DIDS and 5-nitro-2-(3-phenlypropl-amino)benzoic acid, caused a voltage-dependent block of the outwardly rectifying Cl current, inhibition occurring primarily at depolarized potentials. On exposure to hypotonic solution, the slope conductance significantly increased at the resting membrane potential (−70 mV) from 1.2 ± 0.2 to 2.0 ± 0.4 nS and at the slow-wave plateau potential (−35 mV) from 2.1 ± 0.3 to 5.0 ± 1.0 nS. The current was constitutively active in ICC and contributed to the resting membrane potential and excitability at the slow-wave plateau. In conclusion, swelling or volume change will depolarize ICC through activation of outwardly rectifying chloride channels, thereby increasing cell excitability.

Publisher

American Physiological Society

Subject

Physiology (medical),Gastroenterology,Hepatology,Physiology

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