N. Darvish et al., DIVERSE MODULATIONS OF CHLORIDE CHANNELS IN RENAL PROXIMAL TUBULES, American journal of physiology. Renal, fluid and electrolyte physiology, 36(5), 1994, pp. 716-724
Cl--selective channels were detected and characterized in apical membr
anes of cultured rat renal proximal convoluted tubule cells (PCT) usin
g patch-clamping methods. Subpopulations of Cl- channels modulated by
cyclic nucleotides, Ca2+, or voltage were identified. Two different 30
-pS, voltage-independent, Cl- channels modulated by adenosine 3',5'-cy
clic monophosphate (cAMP) or Ca2+ were seen most frequently. The cAMP-
dependent channel was activated by membrane-permeable analogues of cAM
P, dibutyryl-cAMP or 8-bromo-cAMP. Catalytic subunit of protein kinase
A (PKA) applied to detached inside-out patches, activated the channel
as well, suggesting activation via phosphorylation. Channel activity
was blocked by 4,4'-diisothiocyano stilbene-2,2'-disulfonic acid, by 4
,4-dinitrostilbene-2,2-disulfonic acid, and by SCN-. Permeability sequ
ence for different halides was Cl- > I > F with a Cl--to-cation permea
bility ratio (P-Cl/P-cation of 7:1. The Ca2+-sensitive channel was not
activated by cAMP nor by PKA. A third anionic selective channel encou
ntered infrequently is voltage dependent and has a unitary conductance
of 145 pS, with a P-Cl/P-cation value of 9:1. This diversity of Cl- c
hannels may underlie the rich repertoire of physiological functions at
tributed to Cl- channels.