Tyrosine kinase inhibitors and ATP modulate the conversion of smooth muscle L-type Ca2+ channels toward a second open state

Shinsuke Nakayama, Yasushi Ito, Shinji Sato, Atsushi Kamijo, Hong Nian Liu, Shunichi Kajioka

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Properties of smooth and cardiac L-type Ca2+ channels differ prominently in several physiological aspects, including sympathetic modulation. To assess the possible underlying mechanisms, we applied the whole cell patch-clamp technique to guinea pig detrusor smooth muscle cells, in which only L-type Ca2+ channel currents are observed in practice. During depolarization to large positive potentials, the conformation of the majority of L-type Ca2+ channels is converted from the normal (O1) to a second open state (O2), which undergoes little inactivation during depolarization. Extracellular application of genistein, a known tyrosine kinase inhibitor, significantly attenuated the voltage-dependent conversion of Ca 2+ channels to O2, accompanied by reduction of availability, whereas genistin, an inactive analog, had little effect. In the absence of ATP in the patch pipette, intracellular application of either genistein or tyrphostin-47 suppressed the conversion to O2. Computer calculation revealed that the acceleration of the O1 to an inactivated state qualitatively reconstructs the unique effects of PTK inhibitors antagonized by ATP. We concluded that under normal conditions smooth muscle L-type Ca2+ channels are already modulated by tyrosine-kinase and ATP-related mechanism(s) and thereby easily achieve the second conversion, which yields voltage-dependent modulation of L-type Ca2+ current analogous to that in cardiac myocytes during β-adrenoceptor stimulation.

Original languageEnglish
JournalFASEB Journal
Volume20
Issue number9
DOIs
Publication statusPublished - Jul 2006
Externally publishedYes

Fingerprint

smooth muscle
Protein-Tyrosine Kinases
Smooth Muscle
tyrosine
Muscle
phosphotransferases (kinases)
Genistein
Adenosine Triphosphate
Depolarization
calcium
Modulation
genistein
Clamping devices
Electric potential
Patch-Clamp Techniques
Cardiac Myocytes
Adrenergic Receptors
Smooth Muscle Myocytes
Conformations
Guinea Pigs

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Tyrosine kinase inhibitors and ATP modulate the conversion of smooth muscle L-type Ca2+ channels toward a second open state. / Nakayama, Shinsuke; Ito, Yasushi; Sato, Shinji; Kamijo, Atsushi; Liu, Hong Nian; Kajioka, Shunichi.

In: FASEB Journal, Vol. 20, No. 9, 07.2006.

Research output: Contribution to journalArticle

Nakayama, Shinsuke ; Ito, Yasushi ; Sato, Shinji ; Kamijo, Atsushi ; Liu, Hong Nian ; Kajioka, Shunichi. / Tyrosine kinase inhibitors and ATP modulate the conversion of smooth muscle L-type Ca2+ channels toward a second open state. In: FASEB Journal. 2006 ; Vol. 20, No. 9.
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