title: MaxiK channel-triggered negative feedback system is preserved in the urinary bladder smooth muscle from streptozotocin-induced diabetic rats.
abstract: MaxiK channel, the large-conductance Ca2+-sensitive K+ channel, facilitates a negative feedback mechanism to oppose excitation and contraction in various types of smooth muscles including urinary bladder smooth muscle (UBSM). In this study, we investigated how the contribution of MaxiK channel to the regulation of basal UBSM mechanical activity is altered in streptozotocin-induced diabetic rats. Although the urinary bladder preparations from both control and diabetic rats were almost quiescent in their basal mechanical activities, they generated spontaneous rhythmic contractions in response to a MaxiK channel blocker, iberiotoxin (IbTx). The effect of IbTx on the mechanical activity was significantly greater in diabetic rat than in control animal. Similarly, the basal mechanical activity was increased with apamin, an inhibitor for some types of small conductance Ca2+-sensitive K+ channels, and this effect was more pronounced for diabetic rat. However, in both control and diabetic animals, IbTx action was stronger than that of apamin. Diabetes also enhanced the responses to BayK 8644, an L-type Ca2+ channel agonist. The extent of this enhancement in diabetic bladder vs. control was, however, almost the same as that attained with IbTx. Expression levels for MaxiK channel as well as apamin-sensitive K+ channels and L-type Ca2+ channel were not altered by diabetes, when determined as their corresponding mRNA levels. These results indicate that diabetes can potentially increase the basal UBSM mechanical activity. However, in diabetic UBSM, the main negative-feedback system triggered by MaxiK channel is still preserved enough to counteract the possible enhancement of this smooth muscle mechanical activity.
authors.affiliation: Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. nakaharat@pharm.kitasato-u.ac.jp
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakahara
authors.forename: Akiko
authors.initials: A
authors.lastname: Mitani
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kubota
authors.forename: Takeshi
authors.initials: T
authors.lastname: Maruko
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Katsuo
authors.initials: K
authors.lastname: Koike
authors.forename: Koki
authors.initials: K
authors.lastname: Shigenobu
authors.forename: Kunio
authors.initials: K
authors.lastname: Ishii
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001483:Base Sequence; D001696:Biomechanical Phenomena; D020746:Calcium Channels, L-Type / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000503:physiopathology*; D005246:Feedback; D066298:In Vitro Techniques; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000503:physiopathology*; D010455:Peptides / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001743:Urinary Bladder / Q000503:physiopathology*
chemical_list: D020746:Calcium Channels, L-Type; D018076:DNA, Complementary; C494842:Kcnma1 protein, rat; C419385:L-type calcium channel alpha(1C); D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C064719:iberiotoxin