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.