BK channel activation by NS11021 decreases excitability and contractility of urinary bladder smooth muscle
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BK channel activation by NS11021 decreases excitability and contractility of urinary bladder smooth muscle. / Layne, Jeffrey J; Nausch, Bernhard; Olesen, Søren-Peter; Nelson, Mark T.
I: American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, Bind 298, Nr. 2, 2009, s. R378-84.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - BK channel activation by NS11021 decreases excitability and contractility of urinary bladder smooth muscle
AU - Layne, Jeffrey J
AU - Nausch, Bernhard
AU - Olesen, Søren-Peter
AU - Nelson, Mark T
N1 - Keywords: Action Potentials; Animals; Electric Stimulation; Electrophysiology; Guinea Pigs; Large-Conductance Calcium-Activated Potassium Channels; Male; Muscle Contraction; Muscle, Smooth; Patch-Clamp Techniques; Peptides; Potassium Channel Blockers; Tetrazoles; Thiourea; Urinary Bladder
PY - 2009
Y1 - 2009
N2 - Large-conductance Ca(2+)-activated potassium (BK) channels play an important role in regulating the function and activity of urinary bladder smooth muscle (UBSM), and the loss of BK channel function has been shown to increase UBSM excitability and contractility. However, it is not known whether activation of BK channels has the converse effect of reducing UBSM excitability and contractility. Here, we have sought to investigate this possibility by using the novel BK channel opener NS11021. NS11021 (3 microM) caused an approximately threefold increase in both single BK channel open probability (P(o)) and whole cell BK channel currents. The frequency of spontaneous action potentials in UBSM strips was reduced by NS11021 from a control value of 20.9 + or - 5.9 to 10.9 + or - 3.7 per minute. NS11021 also reduced the force of UBSM spontaneous phasic contractions by approximately 50%, and this force reduction was blocked by pretreatment with the BK channel blocker iberiotoxin. NS11021 (3 microM) had no effect on contractions evoked by nerve stimulation. These findings indicate that activating BK channels reduces the force of UBSM spontaneous phasic contractions, principally through decreasing the frequency of spontaneous action potentials.
AB - Large-conductance Ca(2+)-activated potassium (BK) channels play an important role in regulating the function and activity of urinary bladder smooth muscle (UBSM), and the loss of BK channel function has been shown to increase UBSM excitability and contractility. However, it is not known whether activation of BK channels has the converse effect of reducing UBSM excitability and contractility. Here, we have sought to investigate this possibility by using the novel BK channel opener NS11021. NS11021 (3 microM) caused an approximately threefold increase in both single BK channel open probability (P(o)) and whole cell BK channel currents. The frequency of spontaneous action potentials in UBSM strips was reduced by NS11021 from a control value of 20.9 + or - 5.9 to 10.9 + or - 3.7 per minute. NS11021 also reduced the force of UBSM spontaneous phasic contractions by approximately 50%, and this force reduction was blocked by pretreatment with the BK channel blocker iberiotoxin. NS11021 (3 microM) had no effect on contractions evoked by nerve stimulation. These findings indicate that activating BK channels reduces the force of UBSM spontaneous phasic contractions, principally through decreasing the frequency of spontaneous action potentials.
U2 - 10.1152/ajpregu.00458.2009
DO - 10.1152/ajpregu.00458.2009
M3 - Journal article
C2 - 19923353
VL - 298
SP - R378-84
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6119
IS - 2
ER -
ID: 18764868