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Effects of calmodulin antagonists on calcium‐activated potassium channels in pregnant rat myometrium
Author(s) -
Kihira M.,
Matsuzawa K.,
Tokuno H.,
Tomita T.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb15808.x
Subject(s) - calmodulin , myometrium , trifluoperazine , chemistry , potassium channel , calcium , biophysics , calcium activated potassium channel , endocrinology , medicine , biology , uterus , organic chemistry
1 The effects of W‐7, trifluoperazine, and W‐5 on Ca 2+ ‐activated K + ‐channels were investigated with the inside‐out patch‐clamp method in smooth muscle cells freshly dispersed from pregnant rat myometrium. These drugs are known to have different potencies as calmodulin antagonists. 2 In the presence of 1 μ m Ca 2+ on the cytoplasmic side ([Ca 2+ ] i ), the fraction of time the channel was open (open probability, P o ) was about 0.9 and the calmodulin antagonists (1–30 μ m ) applied to the cytoplasmic face reduced P o to 0.65‐0.55 dose‐dependently. In the presence of 0.1‐0.16 μ m Ca 2+ , when P o was very low (0.02), calmodulin antagonists increased P o . All antagonists used produced almost identical effects at the same concentration. 3 The probability density function of the open time distribution could be described by the sum of two exponentials. W‐7 decreased the time constant of the slow component of distribution and at 30 μ m the slow component disappeared both at 1 and 0.25 μ m [Ca 2+ ] i , reflecting the appearance of flickering channel activity. The probability density function of the closed time distribution could be fitted with three exponentials. The time constants of these components were not significantly altered by W‐7. 4 Internally applied calmodulin (1–5 μ m ) did not produce any significant effect on channel activity. 5 The effects of calmodulin antagonists are considered to be due to a direct action of these compounds on the channel, and suggest that channel activation by Ca 2+ is not mediated by calmodulin.