![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
T Asai, S Pelzer and TF McDonald
Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada.
Low-to-moderate concentrations (< or = 3 microM) of forskolin (FSK) stimulated L-type Ca2+ current (ICa,L) and activated Cl- current (IC1) in guinea pig ventricular myocytes investigated under standard whole- cell conditions at 35 degrees. These stimulatory effects reached a steady state after several minutes and smoothly decayed after a short lag period on removal of the drug. Short (2-3 min) exposures to higher concentrations (10-100 microM) of FSK frequently had a multiphasic effect on ICa,L; marked stimulation during the first minute quickly faded during the next 1-2 min, and removal of the drug caused secondary stimulation that lasted for several minutes. Because the amplitude of cAMP-dependent ICl remained stable during the fade and secondary stimulation of ICa,L, the latter modulation of ICa,L seemed to be the result of a cAMP-independent inhibitory action of FSK on Ca2+ channels. Under conditions in which the stimulation of cAMP by FSK was slowed (22 degrees), rapid application of 10-30 microM FSK revealed that inhibition occurred within < 1 sec. In myocytes dialyzed with channel- up-modulating cAMP solution. 0.01-1 microM FSK had no effect on up- modulated currents, whereas high FSK rapidly and reversibly inhibited ICa,L by < or = 42% without affecting ICl. High FSK also inhibited ICa,L in myocytes dialyzed with protein kinase A inhibitor. External but not internal application of the inactive analog 1,9-dideoxy-FSK (30- 100 microM) inhibited basal ICa,L. The inhibition was dependent on holding potential and involved a speeding up of ICa,L inactivation and a slowing of recovery from inactivation. We conclude that FSK inhibits cardiac ICa,L by reducing the availability of Ca2+ channels.
This article has been cited by other articles:
|
|
 |
|
  T. Onda, Y. Hashimoto, M. Nagai, H. Kuramochi, S. Saito, H. Yamazaki, Y. Toya, I. Sakai, C. J. Homcy, K. Nishikawa, et al. Type-specific Regulation of Adenylyl Cyclase. SELECTIVE PHARMACOLOGICAL STIMULATION AND INHIBITION OF ADENYLYL CYCLASE ISOFORMS J. Biol. Chem., December 14, 2001; 276(51): 47785 - 47793. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Lum, H. A. Jaffe, I. T. Schulz, A. Masood, A. RayChaudhury, and R. D. Green Expression of PKA inhibitor (PKI) gene abolishes cAMPmediated protection to endothelial barrier dysfunction Am J Physiol Cell Physiol, September 1, 1999; 277(3): C580 - C588. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Pelzer, Y. You, Y. M. Shuba, and D. J. Pelzer beta -Adrenoceptor-coupled Gs protein facilitates the activation of cAMP-dependent cardiac Cl- current Am J Physiol Heart Circ Physiol, December 1, 1997; 273(6): H2539 - H2548. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
