Transient alkalization caused by activation of
the BK
Ca channels has been reported to be essential
for the activation of proteolytic enzymes and
bacterial killing in the leukocytic phagosomes. We
investigated the effects of high glucose concentrations
on these processes in THP-1 cells. While
E.coli transiently raised the pH of the phagosomes
in THP-1 monocytes, high glucose concentrations
impaired the transient rise of pH in a
dose-and time-dependent manner. Electrophysiological
studies confirmed that the bacteria elicited
a transient K
+ current, and that a high glucose concentration
diminished the current. High glucose
concentrations also inhibited the activation of
cathepsin G in the THP-1 cells. NS1619, a BK
Ca
channel opener, accentuated the transient alkalization
induced by the bacteria, and reversed the
inhibitory effect of high concentrations of glucose.
However, electrophysiological study
revealed that the membrane current differed from
the BK
Ca current. Our findings indicate that high
glucose concentrations impair K
+ channel activation
and the subsequent activation of proteolytic
enzymes in THP-1 monocytes. The precise identity
of the K
+ channel remains unclear, although it
dose not appear to be the BK
Ca. Suppression of the
transient alkalization and activation of proteases
may be one of the mechanisms for bacterial
killing by phagocytes in diabetic patients.
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