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SK channel activation with SKA‐31 decreases excitability and contractility in Guinea pig urinary bladder smooth muscle
Author(s) -
Pandey Rupal,
Parajuli Shankar,
Hristov Kiril,
Petkov Georgi
Publication year - 2011
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.25.1_supplement.1115.16
Subject(s) - apamin , contractility , chemistry , contraction (grammar) , stimulation , inhibitory postsynaptic potential , activator (genetics) , patch clamp , isometric exercise , biophysics , medicine , endocrinology , potassium channel , electrophysiology , biology , receptor
Small (SK) and intermediate (IK) conductance Ca2+‐activated K+ channels have been suggested to be involved in determining the excitability and contractility of detrusor smooth muscle (DSM). We used SKA‐31, a novel SK/IK channel activator to probe the therapeutic potential of SK/IK channel activation to control bladder function. Isometric tension recordings of isolated Guinea pig DSM strips indicated that SKA‐31 (100 nM‐10 μM) significantly inhibited the spontaneous contraction amplitude, muscle force, frequency, and duration. This inhibitory effect was blocked by apamin (1 μM), a selective SK channel inhibitor. SK channel activation with SKA‐31 (3 μM) also reduced the contractions evoked by electrical field stimulation. TRAM‐34 (30 μM), an IK channel selective inhibitor, did not suppress the inhibitory effect of SKA‐31, indicating a role only for the SK channel in detrusor contractility. Using the perforated patch‐clamp technique, we observed that SKA‐31 (10 μM) increased the voltage‐step induced SK currents in freshly isolated DSM cells. In current clamp mode, SKA‐31 (10 μM) hyperpolarized the resting membrane potential by ~3 mV. These effects were blocked by apamin (1 μM). Collectively, our data indicate that activation of SK channels may provide a novel therapeutic approach to control bladder function. Supported by NIH DK084284 & DK083687 to GVP. SKA‐31 is a gift from Dr. Heike Wulff.