Key result
In guinea pig distal colonic crypts, Cl- secretagogues activated small-conductance inwardly rectified K+ channels, whereas K+ secretagogues decreased their open probability.
Secretagogues modulate the activity of a 9-pS inwardly rectifying K+ channel in guinea pig distal colonic crypts, suggesting a role in electrogenic Cl- and K+ secretion.
Findings in guinea pig crypts warrant no clinical action; leaves open whether these channels modulate human colonic secretion.
Cell-attached recordings revealed K(+) channel activity in basolateral membranes of guinea pig distal colonic crypts. Inwardly rectified currents were apparent with a pipette solution containing 140 mM K(+). Single-channel conductance (gamma) was 9 pS at the resting membrane potential. Another inward rectifier with gamma of 19 pS was observed occasionally. At a holding potential of -80 mV, gamma was 21 and 41 pS, respectively. Identity as K(+) channels was confirmed after patch excision by changing the bath ion composition. From reversal potentials, relative permeability of Na(+) over K(+) (P(Na)/P(K)) was 0.02 +/- 0.02, with P(Rb)/P(K) = 1.1 and P(Cl)/P(K) < 0.03. Spontaneous open probability (P(o)) of the 9-pS inward rectifier ((gp)K(ir)) was voltage independent in cell-attached patches. Both a low (P(o) = 0.09 +/- 0.01) and a moderate (P(o) = 0.41 +/- 0.01) activity mode were observed. Excision moved (gp)K(ir) to the medium activity mode; P(o) of (gp)K(ir) was independent of bath Ca(2+) activity and bath acidification. Addition of Cl(-) and K(+) secretagogues altered P(o) of (gp)K(ir). Forskolin or carbachol (10 microM) activated the small-conductance (gp)K(ir) in quiescent patches and increased P(o) in low-activity patches. K(+) secretagogues, either epinephrine (5 microM) or prostaglandin E(2) (100 nM), decreased P(o) of (gp)K(ir) in active patches. This (gp)K(ir) may be involved in electrogenic secretion of Cl(minus sign) and K(+) across the colonic epithelium, which requires a large basolateral membrane K(+) conductance during maximal Cl(-) secretion and, presumably, a lower K(+) conductance during primary electrogenic K(+) secretion.
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Li et al. (2002) studied this question. Cl- and K+ secretagogues (forskolin, carbachol, epinephrine, prostaglandin E2) vs. Baseline (quiescent or active patches) was evaluated on K+ channel open probability (Po) and conductance. In guinea pig distal colonic crypts, Cl- secretagogues activated small-conductance inwardly rectified K+ channels, whereas K+ secretagogues decreased their open probability.
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