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Pharmacological block of K Ca 1.1 channel increases the amplitude of nerve‐evoked contractions induced by electrical field stimulation in human detrusor smooth muscle
Author(s) -
Petkov Georgi V.,
Kellett Whitney F.,
Rovner Eric S.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.986.9
Subject(s) - iberiotoxin , chemistry , purinergic receptor , stimulation , medicine , endocrinology , cholinergic , potassium channel , adenosine , biochemistry
We have previously identified the K Ca 1.1 channel as a major player in human detrusor smooth muscle (HDSM) contractility. Here, we examined the contribution of K Ca 1.1 channels in the nerve‐evoked contractions of isolated HDSM strips. HDSM tissues were obtained from patient‐donors during open surgeries (n–number of strips; N–number of patients). Nerve‐evoked contractions were generated by increasing electrical field stimulation (EFS) frequencies (3.5–50 Hz). Blocking the K Ca 1.1 channel with its specific inhibitor, iberiotoxin (200 nM), caused a statistically significant increase in the nerve‐evoked contraction amplitude at all stimulation frequencies (n=12, N=7). In the presence of 10 μM suramin and 10 μM α , β‐meth‐ATP, iberiotoxin (200 nM) also caused a statistically significant increase in the cholinergic component of the nerve‐evoked contractions (n=10, N=8). In the presence of 1 μM atropine, iberiotoxin (200 nM) still caused a statistically significant increase in the purinergic component of the nerve‐evoked contractions (n=6, N=5). Under block of the K Ca 1.1 channel (200 nM iberiotoxin), the maximum response of the purinergic component was almost doubled. Time‐controls for each experimental series confirmed the stability of the preparations (n=5–7, N=4). The data indicate that the K Ca 1.1 channels oppose nerve‐evoked contractions in HDSM. Supported by NIH DK084284 and DK070909 to G. V. Petkov.