MECHANISMS OF BETA-ADRENERGIC STIMULATION OF CARDIAC CA2-TIME MARKOV ANALYSIS OF SLOW GATING( CHANNELS REVEALED BY DISCRETE)

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.