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Interaction Between Store‐Operated Non‐Selective Cation Channels and the Na + ‐Ca 2+ Exchanger During Secretion in the Rat Colon
Author(s) -
Seip G.,
Schultheiss G.,
Kocks S. L.,
Diener M.
Publication year - 2001
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/eph8602243
Subject(s) - chemistry , divalent , extracellular , biophysics , conductance , intracellular , carbachol , reversal potential , patch clamp , ion transporter , ion exchange , stimulation , pipette , inorganic chemistry , biochemistry , ion , membrane , medicine , receptor , mathematics , organic chemistry , combinatorics , biology
The properties of capacitative Ca 2+ influx were studied using the whole‐cell patch‐clamp technique in crypts isolated from rat distal colon. Store‐operated cation influx was evoked by increasing the intracellular buffering capacity for Ca 2+ in the pipette solution; contamination by Cl − currents was reduced by the use of NMDG gluconate as the main electrolyte in the pipette solution. The permeability of the non‐selective cation conductance stimulated by store depletion had the following sequence for monovalent cations: Cs + > Na + ≥ Li + . The store‐operated conductance is permeable to Na + and Ca 2+ , but in contrast to Na + , Ca 2+ also exerts a (feedback) inhibition on its own influx. Other divalent cations shared this inhibitory action with the sequence: Ca 2+ ≥ Mg 2+ ≥ Ba 2+ ≥ Sr 2+ . Fura‐2 experiments revealed that replacement of extracellular Na + by NMDG + induced an increase in the intracellular Ca 2+ concentration, which was suppressed by the Na + ‐Ca 2+ exchange inhibitor, dichlorobenzamil, indicating the presence of a Na + ‐Ca 2+ exchanger within the colonic crypt cells. In Ussing chamber experiments dichlorobenzamil induced an increase in short‐circuit current (I sc ) in the majority of tissues tested indicating that this exchanger acts as a Ca 2+ ‐extruding transporter under physiological conditions. When Ca 2+ ‐dependent anion secretion was stimulated by the acetylcholine analogue carbachol, dichlorobenzamil no longer evoked an increase in I sc , indicating that after stimulation of the store‐operated cation conductance the Na + ‐Ca 2+ exchanger is turned off. Therefore, it is concluded that the influx of Na + across the non‐selective store‐operated cation conductance serves to reduce the driving force for Ca 2+ extrusion via the Na + ‐Ca 2+ exchanger and thereby maintains the increase in the intracellular Ca 2+ concentration during induction of secretion.