Extracellular pH and Intracellular Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) Control Cl- Currents in Guinea Pig Detrusor Smooth Muscle Cells.

Extracellular pH and Intracellular Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) Control Cl- Currents in Guinea Pig Detrusor Smooth Muscle Cells. Am J Physiol Cell Physiol. 2019 Oct 02;: Authors: Yarotskyy V, Malysz J, Petkov GV Abstract Cl- channels serve as key regulators of smooth muscle excitability and contractility in vascular, intestinal, and airway cells. We recently reported Cl- conductance in detrusor smooth muscle (DSM) cells. Here, we used the whole-cell patch-clamp technique to further characterize biophysical properties and physiological regulators of Cl- currents in freshly-isolated Guinea pig DSM cells. The Cl- current demonstrated outward rectification arising from voltage-dependent gating of Cl- channels rather than the Cl‑ transmembrane gradient. An exposure of DSM cells to hypotonic extracellular solution (Δ 165mOsm challenge) did not increase the Cl- current providing strong evidence that volume-regulated anion channels do not contribute to the Cl- current in DSM cells. The Cl- current was monotonically dependent on extracellular pH, larger and lower in magnitude at acidic (5.0) and basic pH (8.5) values, respectively. Additionally, intracellularly applied phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) analogue (PI(4,5)P2-diC8) increased the average Cl- current density by approximately three-fold in a voltage-independent manner. The magnitude of the DSM whole-cell Cl- current did not depend on the cell ...
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Tags: Am J Physiol Cell Physiol Source Type: research