L-TYPE CALCIUM CURRENTS OF HUMAN MYOCYTES FROM VENTRICLE OF NONFAILING AND FAILING HEARTS AND FROM ATRIUM

L-type calcium currents were studied in Ventricular myocytes isolated from non-failing hearts, i.e. donor hearts not suitable for transplant ation, and from severely failing hearts, i.e. explanted hearts of orga n recipients, in order to identify possible alterations of the current s in cardiomyopathy. Human atrial myocytes were investigated for compa rative purposes. As deficient production of cyclic AMP might contribut e to the development of cardiac failure, the responses to forskolin, a direct stimulator of adenylyl cyclase, were also studied. The patch-c lamp technique was applied in the single electrode whole-cell mode. Ca lcium currents were similar in myocytes from non-failing and failing h earts: Maximum current-densities were 3.8 v 3.1 pA/pF, and 2.2 pA/pF i n atrial cells. In human ventricular cells, threshold was at -33 mV, m aximum at +6 mV and reversal potential at about + 50 mV, potentials of half-maximum steady-state inactivation -24 mV and -18 mV. The slopes of steady-state inactivation curves were +4.1 mV in myopathic and + 5. 5 mV in non-failing cells. In all myocytes the current inactivated wit h two time constants. a fast one with weak and a slow one with pronoun ced potential dependency. Ventricular or atrial myocytes from patients pretreated with calcium antagonists and untreated did not differ in c urrent density or steady-state inactivation. Forskolin (0.5 mu M) incr eased calcium currents in myocytes from non-failing and failing hearts to the same extent (by 143 and 150%). While beta-adrenoceptor numbers are reported to decline in severely failing myocardium, our data do n ot suggest that alterations of the properties of calcium currents cont ribute to the pathophysiology of heart failure, though the number of i nvestigated hearts is limited due to restricted access to non-failing cardiac tissue. No evidence for impairment of the signal transduction cascade beyond the level of GTP binding proteins was found.