In smooth muscle cells, localized intracellular calcium (Ca²⁺) transients, termed "Ca²⁺ sparks", activate several large-conductance Ca²⁺-activated potassium (K_Ca) channels, resulting in a transient K_Ca current. In some smooth muscle cell types, a significant proportion of Ca²⁺ sparks do not activate K_Cachannels. The goal of this study was to explore mechanisms that underlie fractional Ca²⁺ spark to K_Ca channel coupling. We investigated if membrane depolarization or ryanodine-sensitive Ca²⁺ release (RyR) channel activation modulates coupling in newborn (1-3 day old) porcine cerebral artery myocytes. At steady membrane potentials of -40, 0 and +40 mV, mean transient K_Ca current frequency was ~0.18, 0.43, and 0.26 Hz and K_Ca channel activity (NP_O) at the transient K_Ca current peak was ~4, 12 and 24, respectively. Depolarization between -40 and +40 mV increased K_Ca channel sensitivity to Ca²⁺ sparks and elevated the percentage of Ca²⁺ sparks that activated a transient K_Ca current from 59 to 86%. In a Ca²⁺-free bath solution, or in diltiazem, a voltage-dependent Ca²⁺ channel blocker, steady membrane depolarization between -40 and +40 mV increased transient K_Ca current frequency up to ~1.6-fold. In contrast, caffeine (10µM), a RyR channel activator, increased mean transient K_Ca current frequency, but did not alter Ca²⁺ spark to K_Ca channel coupling. These data indicate that coupling is increased by mechanisms that elevate K_Ca channel sensitivity to Ca²⁺ sparks, but not by RyR channel activation. Overall, K_Ca channel insensitivity to Ca²⁺ sparks is a prominent factor causing fractional Ca²⁺ spark uncoupling in newborn cerebral artery myocytes.