HYPERTONIA ÉS NEPHROLOGIA - eLitMed.hu

2002; 6 (1):3–15. ONTOGENY OF POTASSIUM TRANSPORT IN THE DISTAL NEPHRON 11
The temporal and spatial appearance of ROMK expression
after birth correlates well with our patch clamp analysis of the
apical K + conductance of the differentiating principal cell in
the mid-CCD (19). Apical ROMK was detected in the TALH
at an earlier developmental stage than in the collecting duct.
Functional analysis of the K + transport pathways in the TALH
in the maturing nephron have not been performed. However,
results of micropuncture studies (36) are consistent with
functional immaturity of the loop of Henle in early in life.
Postnatal increases in diluting capacity (37; 55) and
Na-K-ATPase activity (40) in rat TALH have been reported,
suggesting that K + transport pathways in this segment may
undergo developmental regulation. Characterization of these
pathways and the role of apical ROMK in ion transport in the
neonatal segment have yet to be accomplished.
In sum, the results of our investigation suggest it likely that
the postnatal increases in number of conducting apical SK and
Na + channels in the differentiating principal cell are mediated,
at least in part, by increases in abundance of ROMK message
and protein and ENaC subunit proteins. The signal(s)
mediating these developmental events remain to be identified.
rate of
K secretion
(pmol/min.mm)
30
25
20
15
10
5
0
Burg’s perf
5mMTEA
0,5 1,5 3 5-6
#
flox rate (nl/min.mm)
*
Although apical SK channels were not detected by patch
clamp analysis of neonatal principal cells, maxi-K channels
were routinely detected in ~10% of cell-attached patches
obtained in 1- to 5- week-old rabbits (19; 26). The high
conductance (>100 pS) maxi-K channel is rarely open at
physiologic membrane potentials but can be activated by
membrane depolarization, elevation of intracellular Ca 2+
concentration ([Ca 2+ ]i ), membrane stretch or hypoosmotic
stress (56-61). These observations have led to the speculation
that the maxi-K channel, considered not to play a major role in
baseline K + secretion in the CCD, functions in cell volume
regulation (57; 62) and/or flow-mediated K + secretion (59;
61).
To directly examine the contribution of the maxi-K channel
to flow-stimulated K + secretion in the CCD, we examined the
effects of luminal tetraethylammonium (TEA) and charybdotoxin,
both inhibitors of maxi-K (56; 59; 61; 63; 64) but not
SK channels (48; 49), or apamin, an inhibitor of small
conductance Ca 2+ -activated K + channels, on flow-stimulated
net K + secretion in isolated perfused CCDs. In the absence of
TEA, net K + secretion increased 3-fold as the tubular flow rate
rate of
Na absorption
(pmol/min.mm)
140
120
100
80
60
40
20
0
Burg’s perf
5mMTEA
0,5 1,5 3 5-6
flox rate (nl/min.mm)
Figure 9. Flow-stimulation of net K + secretion (left) and Na + absorption (right) in the CCD: effect of luminal TEA. Net
transport (pmol/min.mm) was measured in each tubule at 2-3 flow rates in a symmetrical solution simulating an
ultrafiltrate of rabbit plasma. Data were grouped into flow rate intervals and averaged. Each data point represents the
mean±SEM of 6-11 tubules. In the absence of TEA (black bars, left panel), net K + secretion increased with increasing
flow rate (p