S. Herzig et al., MECHANISMS OF BETA-ADRENERGIC STIMULATION OF CARDIAC CA2-TIME MARKOV ANALYSIS OF SLOW GATING( CHANNELS REVEALED BY DISCRETE), Biophysical journal, 65(4), 1993, pp. 1599-1612
Individual cardiac Ca2+ channels cycle slowly between a mode of gating
in which the channel is available to open, and one in which the chann
el remains silent. The regulation of this multisecond cycling process
by isoproterenol was investigated by single-channel recording and the
development of a discrete-time Markov model that describes the slow sw
itching among modes in terms of (de)phosphorylation reactions. The res
ults provide evidence that isoproterenol increases Ca2+ channel activi
ty by a reciprocal regulatory mechanism: not only is the phosphorylati
on rate of the channel increased, but also the dephosphorylation rate
decreased. The discrete-time Markov formalism should prove useful as a
general tool for understanding the mode switching demonstrated by a n
umber of ionic channels.