Author:

Keywords:

Calcium, Calcium Channels, Cell Line, Electric Conductivity, Extracellular Space, Humans, Hydrogen, Hydrogen-Ion Concentration, Magnesium, Research Support, Non-U.S. Gov't, TRPV Cation Channels, Science & Technology, Life Sciences & Biomedicine, Physiology, proton block, Ca2+ channels, transcellular Ca2+ transport, TRP channel family, INDUCED CURRENT FLUCTUATIONS, CALCIUM-TRANSPORT, PERMEATION, DEPENDENCE, PROTONS, BLOCK, 0606 Physiology, 1106 Human Movement and Sports Sciences, 1116 Medical Physiology, 3101 Biochemistry and cell biology, 3109 Zoology, 3208 Medical physiology

Abstract:

We investigated the effect of extracellular pH on whole-cell currents through the epithelial Ca2+ channel, ECaC, expressed in HEK 293 cells. Both mono- and divalent current densities were significantly smaller at pH 6.0 than at pH 7.4. At pH 8.5 they were slightly larger. Lowering extracellular pH enhanced the slow component of monovalent current activation at negative potentials but had no significant effect on the kinetics of Ca2+ currents. The kinetics of block of monovalent cation current by extracellular Mg2+ was significantly changed at high and low pH. The time constant of the time- and voltage-dependent current component during a voltage step to -140 mV was significantly larger at pH 8.5 than at pH 7.4. At pH 6.0 it was almost absent. The [Mg2+] inhibiting 50% of monovalent current through ECaC at pH 6.0 (IC50) was 323 +/- 23 microM (n = 8), compared with 62 +/- 9 microM (n = 4) at pH 7.4 and 38 +/- 4 microM (n = 8) at pH 8.5. The affinity of ECaC for Ca2+ was also affected by extracellular pH, shifting from 4.8 +/- 0.7 microM (n = 6) at pH 6.0 to 161 +/- 30 nM (n = 5) at pH 7.4 and 425 +/- 117 nM (n = 8) at pH 8.5.