Perforated-patch recording does not enhance effect of 3-isobutyl-1-methylxanthine on cardiac calcium current.
Conventional whole cell voltage-clamp recording results in washout of the cardiac Ca2+ current (ICa) response to the beta-adrenergic agonist isoproterenol (Iso), for reasons which are not clear. When dose-response curves for the phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (IBMX) were compared using perforated-patch vs. conventional whole cell recording in guinea pig ventricular myocytes, the conventional whole cell IBMX responses were unexpectedly larger than the perforated-patch responses. Furthermore, during conventional whole cell recording the response to repeated application of Iso declined rapidly, whereas the IBMX response initially increased and then declined. When pipette [Ca2+] was increased to 10(-7) M, conventional whole cell responses to 300 microM IBMX and 10(-9) M Iso were identical to perforated-patch responses. Thus loss of the Iso response during conventional whole cell recording seems to not be solely due to a washout of some constituent of the adenosine 3',5'-cyclic monophosphate pathway. We suggest that unphysiological intracellular [Ca2+] enhances the relative PDE activity and that this contributes to the rapid decline of the Iso response and the initial enhancement of the IBMX response.
Kawamura
A
A
Department of Physiology and Biophysics, University of Illinois at Chicago 60612-7342.
Wahler
G M
GM
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D003956:Dialysis; D004594:Electrophysiology / Q000379:methods; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D007425:Intracellular Membranes / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009994:Osmolar Concentration
D000266:Adenylyl Imidodiphosphate; D007545:Isoproterenol; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine