Secretory Activation of Basolateral Membrane Cl- Channels in Guinea Pig Distal Colonic Crypts

Cell-attached recordings revealed Cl ⁻ channel activity in basolateral membrane of guinea pig distal colonic crypts isolated from basement membrane. Outwardly rectified currents ( ^gp Cl _or ) were apparent with a single-channel conductance (γ) of 29 pS at resting membrane electrical potential; another outward rectifier with γ of 24 pS was also observed (∼25% of ^gp Cl _or ). At a holding potential of −80 mV γ was 18 pS for both ^gp Cl _or currents, and at +80 mV γ was 67 and 40 pS, respectively. Identity as Cl ⁻ channels was confirmed in excised patches by changing bath ion composition. From reversal potentials, relative permeability of K ⁺ over Cl ⁻ ( P _K / P _Cl ) was 0.07 ± 0.03, with relative permeability of Na ⁺ over Cl ⁻ ( P _Na / P _Cl ) = 0.08 ± 0.04. A second type of Cl ⁻ channel was seen with linear current-voltage ( I-V ) relations ( ^gp Cl _L ), having subtypes with γ of 21, 13, and 8 pS. Epinephrine or forskolin increased the number of open ^gp Cl _or and ^gp Cl _L . Open probabilities ( P _o ) of ^gp Cl _or , ^gp Cl _L21 , and ^gp Cl _L13 were voltage dependent in cell-attached patches, higher at more positive potentials. Kinetics of ^gp Cl _or were more rapid with epinephrine activation than with forskolin activation. Epinephrine increased P _o at the resting membrane potential for ^gp Cl _L13 . Secretagogue activation of these Cl ⁻ channels may contribute to stimulation of electrogenic K ⁺ secretion across colonic epithelium by increasing basolateral membrane Cl ⁻ conductance that permits Cl ⁻ exit after uptake via Na ⁺ -K ⁺ -2Cl ⁻ cotransport.