T. Mewes et U. Ravens, L-TYPE CALCIUM CURRENTS OF HUMAN MYOCYTES FROM VENTRICLE OF NONFAILING AND FAILING HEARTS AND FROM ATRIUM, Journal of Molecular and Cellular Cardiology, 26(10), 1994, pp. 1307-1320
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.